Ghrelin

The etymology of the word is an acronym: GHR (“growth hormone-releasing peptide”) + -lin (“a common hormone suffix”), with an incidental pun on both Proto-Indo-European *gʰreh₁- (“to grow”) and English growling.

It is often referred to as “the hunger hormone”. Also known as lenomorelin (INN), it is a peptide hormone produced by ghrelinergic cells in the gastrointestinal tract which functions as a neuropeptide in the central nervous system.

Besides regulating appetite, ghrelin also plays a significant role in regulating the distribution and rate of use of energy.

When the stomach is empty, ghrelin is secreted. When the stomach is stretched, secretion stops.a It acts on hypothalamic brain cells both to increase hunger, and to increase gastric acid secretion and gastrointestinal motility to prepare the body for food intake.

The receptor for ghrelin, the ghrelin/growth hormone secretagogue receptor (GHS-R), is found on the same cells in the brain as the receptor for leptin, the satiety hormone that has opposite effects from ghrelin.

Ghrelin also plays an important role in regulating reward perception in dopamine neurons that link the ventral tegmental area to the nucleus accumbens (a site that plays a role in processing sexual desire, reward, and reinforcement, and in developing addictions) through its colocalized receptors and interaction with dopamine and acetylcholine.

Ghrelin is encoded by the GHRL gene and is presumably produced from the cleavage of the prepropeptide ghrelin/obestatin. Full-length preproghrelin is homologous to promotilin and both are members of the motilin family.

Ghrelin, a brain-gut peptide, has been proven to exert neuroprotection in different kinds of neurological diseases; however, its role and the potential molecular mechanisms in secondary brain injury (SBI) after intracerebral hemorrhage (ICH) are still unknown. In this study, we investigate whether treatment with ghrelin may attenuate SBI in a murine ICH model, and if so, whether the neuroprotective effects are due to the inhibition of nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation and promotion of nuclear factor-E2-related factor 2 (Nrf2)/antioxidative response element (ARE) signaling pathway. Stereotactically intrastriatal infusion of autologous blood was performed to mimic ICH. Ghrelin was given intraperitoneally immediately following ICH and again 1 h later. Results showed that ghrelin attenuated neurobehavioral deficits, brain edema, hematoma volume, and perihematomal cell death post-ICH. Ghrelin inhibited the NLRP3 inflammasome activation and subsequently suppressed the neuroinflammatory response as evidenced by reduced microglia activation, neutrophil infiltration, and pro-inflammatory mediators release after ICH. Additionally, ghrelin alleviated ICH-induced oxidative stress according to the chemiluminescence of luminol and lucigenin, malondialdehyde (MDA) content, and total superoxide dismutase (SOD) activity assays. These changes were accompanied by upregulation of Nrf2 expression, Nrf2 nuclear accumulation, and enhanced Nrf2 DNA binding activity, as well as by increased expressions of Nrf2 downstream target antioxidative genes, including NAD(P)H quinine oxidoreductase-1 (NQO1), glutathione cysteine ligase regulatory subunit (GCLC), and glutathione cysteine ligase modulatory subunit (GCLM). Together, our data suggested that ghrelin protected against ICH-induced SBI by inhibiting NLRP3 inflammasome activation and promoting Nrf2/ARE signaling pathway ¹⁾.

Continuous infusion of ghrelin increased body mass and food intake, but did not increase muscle mass nor improve muscle function, in a long-term critical illness recovery model. Further studies with pulsatile ghrelin delivery or additional anabolic stimuli may further clarify the utility of ghrelin in survivors of critical illness ²⁾.

2: Muta H, Sugita Y, Furuta T, Shiimura Y, Ohshima K, Nakashima K, Sato K, Morioka M, Abe H, Nozawa T, Fujii Y, Kakita A. Expression of the ghrelin/growth hormone secretagogue receptor axis and its functional role in promoting tumor growth in primary central nervous system lymphomas. Neuropathology. 2020 Jan 10. doi: 10.1111/neup.12634. [Epub ahead of print] PubMed PMID: 31925841.

3: Shao XF, Li B, Shen J, Wang QF, Chen SS, Jiang XC, Qiang D. Ghrelin alleviates traumatic brain injury-induced acute lung injury through pyroptosis/NF-κB pathway. Int Immunopharmacol. 2020 Jan 6;79:106175. doi: 10.1016/j.intimp.2019.106175. [Epub ahead of print] PubMed PMID: 31918060.

4: Ma LY, Liu SF, Du JH, Niu Y, Hou PF, Shu Q, Ma RR, Wu SD, Qu QM, Lv YL. Chronic ghrelin administration suppresses IKK/NF-κB/BACE1 mediated Aβ production in primary neurons and improves cognitive function via upregulation of PP1 in STZ-diabetic rats. Neurobiol Learn Mem. 2020 Jan 2:107155. doi: 10.1016/j.nlm.2019.107155. [Epub ahead of print] PubMed PMID: 31904547.

5: Huang J, Liu W, Doycheva DM, Gamdzyk M, Lu W, Tang J, Zhang JH. Ghrelin attenuates oxidative stress and neuronal apoptosis via GHSR-1α/AMPK/Sirt1/PGC-1α/UCP2 pathway in a rat model of neonatal HIE. Free Radic Biol Med. 2019 Sep;141:322-337. doi: 10.1016/j.freeradbiomed.2019.07.001. Epub 2019 Jul 3. PubMed PMID: 31279091; PubMed Central PMCID: PMC6718314.

6: Gan ZS, Stein SC, Swanson R, Guan S, Garcia L, Mehta D, Smith DH. Blood Biomarkers for Traumatic Brain Injury: A Quantitative Assessment of Diagnostic and Prognostic Accuracy. Front Neurol. 2019 Apr 26;10:446. doi: 10.3389/fneur.2019.00446. eCollection 2019. Review. PubMed PMID: 31105646; PubMed Central PMCID: PMC6498532.

7: Chaudhry SR, Lendvai IS, Muhammad S, Westhofen P, Kruppenbacher J, Scheef L, Boecker H, Scheele D, Hurlemann R, Kinfe TM. Inter-ictal assay of peripheral circulating inflammatory mediators in migraine patients under adjunctive cervical non-invasive vagus nerve stimulation (nVNS): A proof-of-concept study. Brain Stimul. 2019 May - Jun;12(3):643-651. doi: 10.1016/j.brs.2019.01.008. Epub 2019 Jan 19. PubMed PMID: 30745260.

8: Han K, Wang QY, Wang CX, Luan SY, Tian WP, Wang Y, Zhang RY. Ghrelin improves pilocarpine‑induced cerebral cortex inflammation in epileptic rats by inhibiting NF‑κB and TNF‑α. Mol Med Rep. 2018 Oct;18(4):3563-3568. doi: 10.3892/mmr.2018.9381. Epub 2018 Aug 10. PubMed PMID: 30106107; PubMed Central PMCID: PMC6131597.

9: Shao X, Hu Q, Chen S, Wang Q, Xu P, Jiang X. Ghrelin Ameliorates Traumatic Brain Injury by Down-Regulating bFGF and FGF-BP. Front Neurosci. 2018 Jul 5;12:445. doi: 10.3389/fnins.2018.00445. eCollection 2018. PubMed PMID: 30026681; PubMed Central PMCID: PMC6041414.

10: Huang Y, He Z, Gao Y, Lieu L, Yao T, Sun J, Liu T, Javadi C, Box M, Afrin S, Guo H, Williams KW. Phosphoinositide 3-Kinase Is Integral for the Acute Activity of Leptin and Insulin in Male Arcuate NPY/AgRP Neurons. J Endocr Soc. 2018 Apr 26;2(6):518-532. doi: 10.1210/js.2018-00061. eCollection 2018 Jun 1. PubMed PMID: 29850651; PubMed Central PMCID: PMC5961025.

11: He R, Yin Y, Li Y, Li Z, Zhao J, Zhang W. Esophagus-duodenum Gastric Bypass Surgery Improves Glucose and Lipid Metabolism in Mice. EBioMedicine. 2018 Feb;28:241-250. doi: 10.1016/j.ebiom.2018.01.032. Epub 2018 Feb 3. PubMed PMID: 29398599; PubMed Central PMCID: PMC5898028.

12: Veedfald S, Plamboeck A, Hartmann B, Vilsbøll T, Knop FK, Deacon CF, Svendsen LB, Holst JJ. Ghrelin secretion in humans - a role for the vagus nerve? Neurogastroenterol Motil. 2018 Jun;30(6):e13295. doi: 10.1111/nmo.13295. Epub 2018 Feb 2. PubMed PMID: 29392854.

13: Suda Y, Kuzumaki N, Narita M, Hamada Y, Shibasaki M, Tanaka K, Tamura H, Kawamura T, Kondo T, Yamanaka A, Narita M. Effect of ghrelin on the motor deficit caused by the ablation of nigrostriatal dopaminergic cells or the inhibition of striatal dopamine receptors. Biochem Biophys Res Commun. 2018 Feb 19;496(4):1102-1108. doi: 10.1016/j.bbrc.2018.01.145. Epub 2018 Feb 1. PubMed PMID: 29378186.

14: Muhammad S, Chaudhry SR, Yearwood TL, Krauss JK, Kinfe TM. Changes of Metabolic Disorders Associated Peripheral Cytokine/Adipokine Traffic in Non-Obese Chronic Back Patients Responsive to Burst Spinal Cord Stimulation. Neuromodulation. 2018 Jan;21(1):31-37. doi: 10.1111/ner.12708. Epub 2017 Oct 24. PubMed PMID: 29064604.

15: Zan J, Song L, Wang J, Zou R, Hong F, Zhao J, Cheng Y, Xu M. Role of ghrelin in small intestinal motility following pediatric intracerebral hemorrhage in mice. Mol Med Rep. 2017 Nov;16(5):6958-6966. doi: 10.3892/mmr.2017.7468. Epub 2017 Sep 12. PubMed PMID: 28901462.

16: Hashiguchi H, Sheng Z, Routh V, Gerzanich V, Simard JM, Bryan J. Direct versus indirect actions of ghrelin on hypothalamic NPY neurons. PLoS One. 2017 Sep 6;12(9):e0184261. doi: 10.1371/journal.pone.0184261. eCollection 2017. PubMed PMID: 28877214; PubMed Central PMCID: PMC5587286.

18: Liu T, Zhong MW, Liu Y, Huang X, Cheng YG, Wang KX, Liu SZ, Hu SY. Effects of sleeve gastrectomy plus trunk vagotomy compared with sleeve gastrectomy on glucose metabolism in diabetic rats. World J Gastroenterol. 2017 May 14;23(18):3269-3278. doi: 10.3748/wjg.v23.i18.3269. PubMed PMID: 28566886; PubMed Central PMCID: PMC5434432.

19: Zhang X, van den Pol AN. Rapid binge-like eating and body weight gain driven by zona incerta GABA neuron activation. Science. 2017 May 26;356(6340):853-859. doi: 10.1126/science.aam7100. PubMed PMID: 28546212; PubMed Central PMCID: PMC6602535.

20: Yoshii Y, Inoue T, Uemura Y, Iwasaki Y, Yada T, Nakabeppu Y, Noda M. Complexity of Stomach-Brain Interaction Induced by Molecular Hydrogen in Parkinson's Disease Model Mice. Neurochem Res. 2017 Sep;42(9):2658-2665. doi: 10.1007/s11064-017-2281-1. Epub 2017 May 2. PubMed PMID: 28462451.

21: Mondal A, Koyama K, Mikami T, Horita T, Takemi S, Tsuda S, Sakata I, Sakai T. Underlying mechanism of the cyclic migrating motor complex in Suncus murinus: a change in gastrointestinal pH is the key regulator. Physiol Rep. 2017 Jan;5(1). pii: e13105. doi: 10.14814/phy2.13105. PubMed PMID: 28082431; PubMed Central PMCID: PMC5256163.

22: Cheng Y, Wei Y, Yang W, Cai Y, Chen B, Yang G, Shang H, Zhao W. Ghrelin Attenuates Intestinal Barrier Dysfunction Following Intracerebral Hemorrhage in Mice. Int J Mol Sci. 2016 Dec 6;17(12). pii: E2032. PubMed PMID: 27929421; PubMed Central PMCID: PMC5187832.

23: Zhang QJ, Yang CC, Zhang SY, Zhang LH, Li J. Alteration of NPY in hypothalamus and its correlation with leptin and ghrelin during the development of T2DM in a rat model. Springerplus. 2016 Nov 3;5(1):1913. doi: 10.1186/s40064-016-3555-9. eCollection 2016. PubMed PMID: 27867820; PubMed Central PMCID: PMC5095108.

24: Zhang X, van den Pol AN. Hypothalamic arcuate nucleus tyrosine hydroxylase neurons play orexigenic role in energy homeostasis. Nat Neurosci. 2016 Oct;19(10):1341-7. doi: 10.1038/nn.4372. Epub 2016 Aug 22. PubMed PMID: 27548245; PubMed Central PMCID: PMC6402046.

25: Okada Y, Sugita Y, Ohshima K, Morioka M, Komaki S, Miyoshi J, Abe H. Signaling of ghrelin and its functional receptor, the growth hormone secretagogue receptor, promote tumor growth in glioblastomas. Neuropathology. 2016 Dec;36(6):535-543. doi: 10.1111/neup.12315. Epub 2016 Jun 14. PubMed PMID: 27297445.

26: Haass-Koffler CL, Giovenco DE, Lee MR, Zywiak WH, de la Monte SM, Kenna GA, Swift RM, Leggio L. Serum Insulin Levels Are Reduced by Intravenous Ghrelin Administration but Do Not Correlate with Alcohol Craving in Alcohol-Dependent Individuals. Int J Neuropsychopharmacol. 2016 May 21. pii: pyw048. doi: 10.1093/ijnp/pyw048. [Epub ahead of print] PubMed PMID: 27207912; PubMed Central PMCID: PMC5091823.

27: Wu SC, Rau CS, Lu TH, Tzeng SL, Wu YC, Wu CJ, Lin CW, Hsieh CH. Effect of Weight-Reduction in Obese Mice Lacking Toll-Like Receptor 5 and C57BL/6 Mice Fed a Low-Fat Diet. Mediators Inflamm. 2015;2015:852126. doi: 10.1155/2015/852126. Epub 2015 Nov 23. PubMed PMID: 26681840; PubMed Central PMCID: PMC4670872.

28: Haass-Koffler CL, Aoun EG, Swift RM, de la Monte SM, Kenna GA, Leggio L. Leptin levels are reduced by intravenous ghrelin administration and correlated with cue-induced alcohol craving. Transl Psychiatry. 2015 Sep 29;5:e646. doi: 10.1038/tp.2015.140. PubMed PMID: 26418274; PubMed Central PMCID: PMC5545639.

29: Wang J, Guo S, Han L, Fang M, Wang L, Bartsch JW, Li J. Correlation of ghrelin and growth hormone secretagogue receptor expression with clinical features in human pituitary adenomas. Exp Ther Med. 2015 May;9(5):1909-1914. Epub 2015 Mar 11. PubMed PMID: 26136913; PubMed Central PMCID: PMC4471707.

30: Kurita H, Xu KY, Maejima Y, Nakata M, Dezaki K, Santoso P, Yang Y, Arai T, Gantulga D, Muroya S, Lefor AK, Kakei M, Watanabe E, Yada T. Arcuate Na+,K+-ATPase senses systemic energy states and regulates feeding behavior through glucose-inhibited neurons. Am J Physiol Endocrinol Metab. 2015 Aug 15;309(4):E320-33. doi: 10.1152/ajpendo.00446.2014. Epub 2015 Jun 16. PubMed PMID: 26081283.

31: Chen YC, Chiang CF, Wu SK, Chen LF, Hsieh WY, Lin WL. Targeting microbubbles-carrying TGFβ1 inhibitor combined with ultrasound sonication induce BBB/BTB disruption to enhance nanomedicine treatment for brain tumors. J Control Release. 2015 Aug 10;211:53-62. doi: 10.1016/j.jconrel.2015.05.288. Epub 2015 Jun 3. PubMed PMID: 26047759.

32: Steele CA, Powell JL, Kemp GJ, Halford JC, Wilding JP, Harrold JA, Kumar SV, Cuthbertson DJ, Cross AA, Javadpour M, MacFarlane IA, Stancak AA, Daousi C. Cerebral activations during viewing of food stimuli in adult patients with acquired structural hypothalamic damage: a functional neuroimaging study. Int J Obes (Lond). 2015 Sep;39(9):1376-82. doi: 10.1038/ijo.2015.82. Epub 2015 May 14. PubMed PMID: 25971928.

33: Goswami C, Tanaka T, Jogahara T, Sakai T, Sakata I. Motilin stimulates pepsinogen secretion in Suncus murinus. Biochem Biophys Res Commun. 2015 Jul 3;462(3):263-8. doi: 10.1016/j.bbrc.2015.04.129. Epub 2015 May 6. PubMed PMID: 25957475.

34: Lucchi C, Vinet J, Meletti S, Biagini G. Ischemic-hypoxic mechanisms leading to hippocampal dysfunction as a consequence of status epilepticus. Epilepsy Behav. 2015 Aug;49:47-54. doi: 10.1016/j.yebeh.2015.04.003. Epub 2015 Apr 29. PubMed PMID: 25934585.

35: Ibáñez-Costa A, Gahete MD, Rivero-Cortés E, Rincón-Fernández D, Nelson R, Beltrán M, de la Riva A, Japón MA, Venegas-Moreno E, Gálvez MÁ, García-Arnés JA, Soto-Moreno A, Morgan J, Tsomaia N, Culler MD, Dieguez C, Castaño JP, Luque RM. In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features. Sci Rep. 2015 Mar 4;5:8714. doi: 10.1038/srep08714. PubMed PMID: 25737012; PubMed Central PMCID: PMC4649711.

36: Hill NE, Saeed S, Phadke R, Ellis MJ, Chambers D, Wilson DR, Castells J, Morel J, Freysennet DG, Brett SJ, Murphy KG, Singer M. Detailed characterization of a long-term rodent model of critical illness and recovery. Crit Care Med. 2015 Mar;43(3):e84-96. doi: 10.1097/CCM.0000000000000854. PubMed PMID: 25700075.

37: Kucuk A, Bayram F, Ozturk F, Tumturk A, Diri H, Oral S, Tucer B, Durak AC, Kurtsoy A. Evaluation of Aggressive Behavior and Invasive Features of Pituitary Adenomas Using Radiological, Surgical, Clinical and Histopathological Markers. Turk Neurosurg. 2016;26(5):671-7. doi: 10.5137/1019-5149.JTN.13161-14.2. PubMed PMID: 27438615.

38: Sun GX, Ding R, Li M, Guo Y, Fan LP, Yue LS, Li LY, Zhao M. Ghrelin attenuates renal fibrosis and inflammation of obstructive nephropathy. J Urol. 2015 Jun;193(6):2107-15. doi: 10.1016/j.juro.2014.11.098. Epub 2014 Dec 3. PubMed PMID: 25481038.

39: Mear Y, Blanchard MP, Defilles C, Brue T, Figarella-Branger D, Graillon T, Manavela M, Barlier A, Enjalbert A, Thirion S. Ghrelin receptor (GHS-R1a) and its constitutive activity in somatotroph adenomas: a new co-targeting therapy using GHS-R1a inverse agonists and somatostatin analogs. J Clin Endocrinol Metab. 2014 Dec;99(12):E2463-71. doi: 10.1210/jc.2014-2753. PubMed PMID: 25272306.

40: Yakabi K, Harada Y, Takayama K, Ro S, Ochiai M, Iizuka S, Hattori T, Wang L, Taché Y. Peripheral α2-β1 adrenergic interactions mediate the ghrelin response to brain urocortin 1 in rats. Psychoneuroendocrinology. 2014 Dec;50:300-10. doi: 10.1016/j.psyneuen.2014.09.003. Epub 2014 Sep 16. PubMed PMID: 25265283; PubMed Central PMCID: PMC5942202.

41: Hao XK, Wu W, Wang CX, Xie GB, Li T, Wu HM, Huang LT, Zhou ML, Hang CH, Shi JX. Ghrelin alleviates early brain injury after subarachnoid hemorrhage via the PI3K/Akt signaling pathway. Brain Res. 2014 Oct 31;1587:15-22. doi: 10.1016/j.brainres.2014.08.069. Epub 2014 Sep 6. PubMed PMID: 25199591.

42: Reyes-Vidal C, Fernandez JC, Bruce JN, Crisman C, Conwell IM, Kostadinov J, Geer EB, Post KD, Freda PU. Prospective study of surgical treatment of acromegaly: effects on ghrelin, weight, adiposity, and markers of CV risk. J Clin Endocrinol Metab. 2014 Nov;99(11):4124-32. doi: 10.1210/jc.2014-2259. Epub 2014 Aug 19. PubMed PMID: 25137427; PubMed Central PMCID: PMC4223431.

43: Khowailed A, Younan SM, Ashour H, Kamel AE, Sharawy N. Effects of ghrelin on sepsis-induced acute kidney injury: one step forward. Clin Exp Nephrol. 2015 Jun;19(3):419-26. doi: 10.1007/s10157-014-1006-x. Epub 2014 Jul 8. PubMed PMID: 25002019.

44: Leggio L, Zywiak WH, Fricchione SR, Edwards SM, de la Monte SM, Swift RM, Kenna GA. Intravenous ghrelin administration increases alcohol craving in alcohol-dependent heavy drinkers: a preliminary investigation. Biol Psychiatry. 2014 Nov 1;76(9):734-41. doi: 10.1016/j.biopsych.2014.03.019. Epub 2014 Mar 25. PubMed PMID: 24775991; PubMed Central PMCID: PMC4176606.

45: Qi L, Cui X, Dong W, Barrera R, Coppa GF, Wang P, Wu R. Ghrelin protects rats against traumatic brain injury and hemorrhagic shock through upregulation of UCP2. Ann Surg. 2014 Jul;260(1):169-78. doi: 10.1097/SLA.0000000000000328. PubMed PMID: 24670857.

46: Chen YC, Chiang CF, Chen LF, Liang PC, Hsieh WY, Lin WL. Polymersomes conjugated with des-octanoyl ghrelin and folate as a BBB-penetrating cancer cell-targeting delivery system. Biomaterials. 2014 Apr;35(13):4066-81. doi: 10.1016/j.biomaterials.2014.01.042. Epub 2014 Feb 7. PubMed PMID: 24513319.

47: Xu Z, Lv XA, Wang JW, Chen ZP, Qiu HS. Predictive value of early decreased plasma ghrelin level for three-month cognitive deterioration in patients with mild traumatic brain injury. Peptides. 2014 Apr;54:180-5. doi: 10.1016/j.peptides.2014.01.021. Epub 2014 Feb 5. PubMed PMID: 24508379.

48: Patel K, Joharapurkar A, Dhanesha N, Patel V, Kshirsagar S, Raval P, Raval S, Jain MR. Thyroid hormone modulates food intake and glycemia via ghrelin secretion in Zucker fatty rats. Drug Res (Stuttg). 2014 Oct;64(10):523-9. doi: 10.1055/s-0033-1363222. Epub 2013 Dec 19. PubMed PMID: 24357139.

49: Chen YC, Chiang CF, Chen LF, Liao SC, Hsieh WY, Lin WL. Polymersomes conjugated with des-octanoyl ghrelin for the delivery of therapeutic and imaging agents into brain tissues. Biomaterials. 2014 Feb;35(6):2051-65. doi: 10.1016/j.biomaterials.2013.11.051. Epub 2013 Dec 7. PubMed PMID: 24315575.

50: Kasacka I, Arciszewski M, Łebkowski W. Extraordinary level of hormone and number of ghrelin cells in the stomach and duodenum of an obese woman. Acta Histochem. 2014 Jan;116(1):230-4. doi: 10.1016/j.acthis.2013.05.007. Epub 2013 Jun 24. PubMed PMID: 23806576.

51: Miyano Y, Sakata I, Kuroda K, Aizawa S, Tanaka T, Jogahara T, Kurotani R, Sakai T. The role of the vagus nerve in the migrating motor complex and ghrelin- and motilin-induced gastric contraction in suncus. PLoS One. 2013 May 28;8(5):e64777. doi: 10.1371/journal.pone.0064777. Print 2013. PubMed PMID: 23724093; PubMed Central PMCID: PMC3665597.

52: Soeki T, Niki T, Uematsu E, Bando S, Matsuura T, Kusunose K, Ise T, Ueda Y, Tomita N, Yamaguchi K, Koshiba K, Yagi S, Fukuda D, Taketani Y, Iwase T, Yamada H, Wakatsuki T, Akaike M, Shimabukuro M, Kishimoto I, Kangawa K, Sata M. Ghrelin protects the heart against ischemia-induced arrhythmias by preserving connexin-43 protein. Heart Vessels. 2013 Nov;28(6):795-801. doi: 10.1007/s00380-013-0333-2. Epub 2013 Mar 15. PubMed PMID: 23494606.

53: Porporato PE, Filigheddu N, Reano S, Ferrara M, Angelino E, Gnocchi VF, Prodam F, Ronchi G, Fagoonee S, Fornaro M, Chianale F, Baldanzi G, Surico N, Sinigaglia F, Perroteau I, Smith RG, Sun Y, Geuna S, Graziani A. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice. J Clin Invest. 2013 Feb;123(2):611-22. doi: 10.1172/JCI39920. Epub 2013 Jan 2. PubMed PMID: 23281394; PubMed Central PMCID: PMC3561827.

54: Inoue Y, Nakahara K, Maruyama K, Suzuki Y, Hayashi Y, Kangawa K, Murakami N. Central and peripheral des-acyl ghrelin regulates body temperature in rats. Biochem Biophys Res Commun. 2013 Jan 4;430(1):278-83. doi: 10.1016/j.bbrc.2012.10.137. Epub 2012 Nov 15. PubMed PMID: 23159626.

55: Date Y. Ghrelin and the vagus nerve. Methods Enzymol. 2012;514:261-9. doi: 10.1016/B978-0-12-381272-8.00016-7. PubMed PMID: 22975058.

56: Kim HH, Park MI, Lee SH, Hwang HY, Kim SE, Park SJ, Moon W. Effects of vagus nerve preservation and vagotomy on peptide YY and body weight after subtotal gastrectomy. World J Gastroenterol. 2012 Aug 14;18(30):4044-50. doi: 10.3748/wjg.v18.i30.4044. PubMed PMID: 22912556; PubMed Central PMCID: PMC3420002.

57: Ogawa N, Ito M, Yamaguchi H, Shiuchi T, Okamoto S, Wakitani K, Minokoshi Y, Nakazato M. Intestinal fatty acid infusion modulates food preference as well as calorie intake via the vagal nerve and midbrain-hypothalamic neural pathways in rats. Metabolism. 2012 Sep;61(9):1312-20. doi: 10.1016/j.metabol.2012.02.011. Epub 2012 Mar 24. PubMed PMID: 22445513.

58: Markaki E, Ellul J, Kefalopoulou Z, Trachani E, Theodoropoulou A, Kyriazopoulou V, Constantoyannis C. The role of ghrelin, neuropeptide Y and leptin peptides in weight gain after deep brain stimulation for Parkinson's disease. Stereotact Funct Neurosurg. 2012;90(2):104-12. doi: 10.1159/000335045. Epub 2012 Mar 2. PubMed PMID: 22398667.

59: Erşahın M, Toklu HZ, Erzık C, Akakin D, Tetık S, Sener G, Yeğen BC. Ghrelin alleviates spinal cord injury in rats via its anti-inflammatory effects. Turk Neurosurg. 2011;21(4):599-605. doi: 10.5137/1019-5149.JTN .4736-11.0. PubMed PMID: 22194122.

60: Pawlik MW, Obuchowicz R, Biernat J, Szczepanski W, Pajdo R, Kwiecień S, Brzozowski T, Konturek SJ, Pawlik WW. Effects of peripherally and centrally applied ghrelin in the pathogenesis of ischemia-reperfusion induced injury of the small intestine. J Physiol Pharmacol. 2011 Aug;62(4):429-39. PubMed PMID: 22100844.

61: Rajan D, Wu R, Shah KG, Jacob A, Coppa GF, Wang P. Human ghrelin protects animals from renal ischemia-reperfusion injury through the vagus nerve. Surgery. 2012 Jan;151(1):37-47. doi: 10.1016/j.surg.2011.06.027. Epub 2011 Sep 22. PubMed PMID: 21943641; PubMed Central PMCID: PMC3237861.

62: Huang L, Qiu B, Yuan L, Zheng L, Li Q, Zhu S. Influence of fasting, insulin and glucose on ghrelin in the dorsal vagal complex in rats. J Endocrinol. 2011 Dec;211(3):257-62. doi: 10.1530/JOE-11-0147. Epub 2011 Sep 19. PubMed PMID: 21930685.

63: Yang CG, Qiu WC, Wang ZG, Yu S, Yan J, Zheng Q. Down-regulation of ghrelin receptors in the small intestine delays small intestinal transit in vagotomized rats. Mol Med Rep. 2011 Nov-Dec;4(6):1061-5. doi: 10.3892/mmr.2011.571. Epub 2011 Aug 24. PubMed PMID: 21874246.

64: Shimizu S, Akiyama T, Kawada T, Sonobe T, Kamiya A, Shishido T, Tokudome T, Hosoda H, Shirai M, Kangawa K, Sugimachi M. Centrally administered ghrelin activates cardiac vagal nerve in anesthetized rabbits. Auton Neurosci. 2011 Jul 5;162(1-2):60-5. doi: 10.1016/j.autneu.2011.04.001. Epub 2011 May 2. PubMed PMID: 21543266.

65: Liu Z, Wang F, Li ZZ, Qi JH, Xu WZ, Zhang PS, Sun T. [Expression of neuropeptides ghrelin and Nesfatin-1 in kainic acid kindling rats]. Zhonghua Yi Xue Za Zhi. 2011 Feb 22;91(7):496-500. Chinese. PubMed PMID: 21418984.

66: Morozumi N, Hanada T, Habara H, Yamaki A, Furuya M, Nakatsuka T, Inomata N, Minamitake Y, Ohsuye K, Kangawa K. The role of C-terminal part of ghrelin in pharmacokinetic profile and biological activity in rats. Peptides. 2011 May;32(5):1001-7. doi: 10.1016/j.peptides.2011.01.021. Epub 2011 Feb 1. PubMed PMID: 21291937.

67: Ceranowicz D, Warzecha Z, Dembinski A, Ceranowicz P, Cieszkowski J, Kusnierz-Cabala B, Tomaszewska R, Kuwahara A, Kato I. Role of hormonal axis, growth hormone - IGF-1, in the therapeutic effect of ghrelin in the course of cerulein-induced acute pancreatitis. J Physiol Pharmacol. 2010 Oct;61(5):599-606. PubMed PMID: 21081804.

68: Al-Massadi O, Trujillo ML, Señaris R, Pardo M, Castelao C, Casanueva FF, Seoane LM. The vagus nerve as a regulator of growth hormone secretion. Regul Pept. 2011 Jan 17;166(1-3):3-8. doi: 10.1016/j.regpep.2010.10.008. Epub 2010 Nov 5. PubMed PMID: 21056594.

69: Tian C, Ye F, Wang L, Deng Y, Dong Y, Wang X, Xu T, Lei T, Wang X. Nitric oxide inhibits ghrelin-induced cell proliferation and ERK1/2 activation in GH3 cells. Endocrine. 2010 Dec;38(3):412-6. doi: 10.1007/s12020-010-9402-9. Epub 2010 Oct 23. PubMed PMID: 20972719.

70: Al-Massadi O, Gabellieri E, Trujillo ML, Señaris R, Pagotto U, Pasquali R, Casanueva FF, Seoane LM. Peripheral endocannabinoid system-mediated actions of rimonabant on growth hormone secretion are ghrelin-dependent. J Neuroendocrinol. 2010 Nov;22(11):1127-36. doi: 10.1111/j.1365-2826.2010.02065.x. PubMed PMID: 20807320.

71: Huda MS, Mani H, Dovey T, Halford JC, Boyland E, Daousi C, Wilding JP, Pinkney J. Ghrelin inhibits autonomic function in healthy controls, but has no effect on obese and vagotomized subjects. Clin Endocrinol (Oxf). 2010 Nov;73(5):678-85. doi: 10.1111/j.1365-2265.2010.03865.x. PubMed PMID: 20738316.

72: Cheyuo C, Wu R, Zhou M, Jacob A, Coppa G, Wang P. Ghrelin suppresses inflammation and neuronal nitric oxide synthase in focal cerebral ischemia via the vagus nerve. Shock. 2011 Mar;35(3):258-65. doi: 10.1097/SHK.0b013e3181f48a37. PubMed PMID: 20720512.

73: Nakahara K, Okame R, Katayama T, Miyazato M, Kangawa K, Murakami N. Nutritional and environmental factors affecting plasma ghrelin and leptin levels in rats. J Endocrinol. 2010 Oct;207(1):95-103. doi: 10.1677/JOE-10-0062. Epub 2010 Jul 14. PubMed PMID: 20631048.

74: Kamiji MM, Troncon LE, Antunes-Rodrigues J, Elias LL, de Castro M, Oliveira RB. Ghrelin and PYY(3-36) in gastrectomized and vagotomized patients: relations with appetite, energy intake and resting energy expenditure. Eur J Clin Nutr. 2010 Aug;64(8):845-52. doi: 10.1038/ejcn.2010.88. Epub 2010 May 19. PubMed PMID: 20485299.

75: Tian C, Ye F, Xu T, Wang S, Wang X, Wang H, Wan F, Lei T. GHRP-6 induces CREB phosphorylation and growth hormone secretion via a protein kinase Csigma-dependent pathway in GH3 cells. J Huazhong Univ Sci Technolog Med Sci. 2010 Apr;30(2):183-7. doi: 10.1007/s11596-010-0210-5. Epub 2010 Apr 21. PubMed PMID: 20407870.

76: Erşahin M, Toklu HZ, Erzik C, Cetinel S, Akakin D, Velioğlu-Oğünç A, Tetik S, Ozdemir ZN, Sener G, Yeğen BC. The anti-inflammatory and neuroprotective effects of ghrelin in subarachnoid hemorrhage-induced oxidative brain damage in rats. J Neurotrauma. 2010 Jun;27(6):1143-55. doi: 10.1089/neu.2009.1210. PubMed PMID: 20205513.

77: Xu T, Ye F, Wang B, Tian C, Wang S, Shu K, Guo D, Lei T. Elevation of growth hormone secretagogue receptor type 1a mRNA expression in human growth hormone-secreting pituitary adenoma harboring G protein alpha subunit mutation. Neuro Endocrinol Lett. 2010;31(1):147-54. PubMed PMID: 20150876.

78: Adachi S, Takiguchi S, Okada K, Yamamoto K, Yamasaki M, Miyata H, Nakajima K, Fujiwara Y, Hosoda H, Kangawa K, Mori M, Doki Y. Effects of ghrelin administration after total gastrectomy: a prospective, randomized, placebo-controlled phase II study. Gastroenterology. 2010 Apr;138(4):1312-20. doi: 10.1053/j.gastro.2009.12.058. Epub 2010 Jan 11. PubMed PMID: 20060830.

79: Jaskula M, Wasko R, Komarowska H, Dziubandowska A, Sowinski J. Serum ghrelin levels and disturbances of the lipid profile in patients with acromegaly. Neuro Endocrinol Lett. 2009;30(2):245-55. PubMed PMID: 19675514.

80: van den Pol AN, Yao Y, Fu LY, Foo K, Huang H, Coppari R, Lowell BB, Broberger C. Neuromedin B and gastrin-releasing peptide excite arcuate nucleus neuropeptide Y neurons in a novel transgenic mouse expressing strong Renilla green fluorescent protein in NPY neurons. J Neurosci. 2009 Apr 8;29(14):4622-39. doi: 10.1523/JNEUROSCI.3249-08.2009. PubMed PMID: 19357287; PubMed Central PMCID: PMC2745949.

81: Trivin C, Busiah K, Mahlaoui N, Recasens C, Souberbielle JC, Zerah M, Sainte-Rose C, Brauner R. Childhood craniopharyngioma: greater hypothalamic involvement before surgery is associated with higher homeostasis model insulin resistance index. BMC Pediatr. 2009 Apr 2;9:24. doi: 10.1186/1471-2431-9-24. PubMed PMID: 19341477; PubMed Central PMCID: PMC2675525.

82: Kudoh K, Shibata C, Funayama Y, Fukushima K, Ueno T, Hayashi K, Inui A, Bowers CY, Sasaki I. The effect of growth hormone releasing peptide-2 on upper gastrointestinal contractile activity and food intake in conscious dogs. J Gastroenterol. 2009;44(4):297-304. doi: 10.1007/s00535-009-0025-y. Epub 2009 Mar 7. PubMed PMID: 19271111.

83: Kobashi M, Yanagihara M, Fujita M, Mitoh Y, Matsuo R. Fourth ventricular administration of ghrelin induces relaxation of the proximal stomach in the rat. Am J Physiol Regul Integr Comp Physiol. 2009 Feb;296(2):R217-23. doi: 10.1152/ajpregu.00878.2007. Epub 2008 Nov 26. PubMed PMID: 19036830.

84: Yakabi K, Kawashima J, Kato S. Ghrelin and gastric acid secretion. World J Gastroenterol. 2008 Nov 7;14(41):6334-8. Review. PubMed PMID: 19009648; PubMed Central PMCID: PMC2766114.

85: Erlanson-Albertsson C, Lindqvist A. Vagotomy and accompanying pyloroplasty down-regulates ghrelin mRNA but does not affect ghrelin secretion. Regul Pept. 2008 Nov 29;151(1-3):14-8. doi: 10.1016/j.regpep.2008.08.006. Epub 2008 Sep 5. PubMed PMID: 18804492.

86: Taniguchi H, Ariga H, Zheng J, Ludwig K, Mantyh C, Pappas TN, Takahashi T. Endogenous ghrelin and 5-HT regulate interdigestive gastrointestinal contractions in conscious rats. Am J Physiol Gastrointest Liver Physiol. 2008 Aug;295(2):G403-11. doi: 10.1152/ajpgi.90260.2008. Epub 2008 Jun 19. PubMed PMID: 18566321.

87: Takeda H, Sadakane C, Hattori T, Katsurada T, Ohkawara T, Nagai K, Asaka M. Rikkunshito, an herbal medicine, suppresses cisplatin-induced anorexia in rats via 5-HT2 receptor antagonism. Gastroenterology. 2008 Jun;134(7):2004-13. doi: 10.1053/j.gastro.2008.02.078. Epub 2008 Feb 29. PubMed PMID: 18439428.

88: Wu R, Dong W, Ji Y, Zhou M, Marini CP, Ravikumar TS, Wang P. Orexigenic hormone ghrelin attenuates local and remote organ injury after intestinal ischemia-reperfusion. PLoS One. 2008 Apr 23;3(4):e2026. doi: 10.1371/journal.pone.0002026. PubMed PMID: 18431503; PubMed Central PMCID: PMC2295264.

89: Kapica M, Zabielska M, Puzio I, Jankowska A, Kato I, Kuwahara A, Zabielski R. Obestatin stimulates the secretion of pancreatic juice enzymes through a vagal pathway in anaesthetized rats - preliminary results. J Physiol Pharmacol. 2007 Aug;58 Suppl 3:123-30. PubMed PMID: 17901588.

90: Aydin M, Canpolat S, Kuloğlu T, Yasar A, Colakoglu N, Kelestimur H. Effects of pinealectomy and exogenous melatonin on ghrelin and peptide YY in gastrointestinal system and neuropeptide Y in hypothalamic arcuate nucleus: immunohistochemical studies in male rats. Regul Pept. 2008 Feb 7;146(1-3):197-203. Epub 2007 Sep 14. PubMed PMID: 17936373.

91: Hosoda H, Kangawa K. The autonomic nervous system regulates gastric ghrelin secretion in rats. Regul Pept. 2008 Feb 7;146(1-3):12-8. Epub 2007 Jul 31. PubMed PMID: 17720259.

92: Sato M, Nakahara K, Miyazato M, Kangawa K, Murakami N. Regulation of GH secretagogue receptor gene expression in the rat nodose ganglion. J Endocrinol. 2007 Jul;194(1):41-6. PubMed PMID: 17592019.

93: Seoane LM, Al-Massadi O, Caminos JE, Tovar SA, Dieguez C, Casanueva FF. Sensory stimuli directly acting at the central nervous system regulate gastric ghrelin secretion. an ex vivo organ culture study. Endocrinology. 2007 Aug;148(8):3998-4006. Epub 2007 May 10. PubMed PMID: 17495002.

94: Kawamata T, Inui A, Hosoda H, Kangawa K, Hori T. Perioperative plasma active and total ghrelin levels are reduced in acromegaly when compared with in nonfunctioning pituitary tumours even after normalization of serum GH. Clin Endocrinol (Oxf). 2007 Jul;67(1):140-4. Epub 2007 Apr 27. PubMed PMID: 17466003.

95: Nawrot-Porabka K, Jaworek J, Leja-Szpak A, Szklarczyk J, Macko M, Kot M, Mitis-Musioł M, Konturek SJ, Pawlik WW. The effect of luminal ghrelin on pancreatic enzyme secretion in the rat. Regul Pept. 2007 Oct 4;143(1-3):56-63. Epub 2007 Mar 14. PubMed PMID: 17462749.

96: Kapica M, Laubitz D, Puzio I, Jankowska A, Zabielski R. The ghrelin pentapeptide inhibits the secretion of pancreatic juice in rats. J Physiol Pharmacol. 2006 Dec;57(4):691-700. PubMed PMID: 17229991.

97: Murray CD, Booth CE, Bulmer DC, Kamm MA, Emmanuel AV, Winchester WJ. Ghrelin augments afferent response to distension in rat isolated jejunum. Neurogastroenterol Motil. 2006 Dec;18(12):1112-20. PubMed PMID: 17109695.

98: Dembiński A, Warzecha Z, Ceranowicz P, Cieszkowski J, Pawlik WW, Tomaszewska R, Kuśnierz-Cabala B, Naskalski JW, Kuwahara A, Kato I. Role of growth hormone and insulin-like growth factor-1 in the protective effect of ghrelin in ischemia/reperfusion-induced acute pancreatitis. Growth Horm IGF Res. 2006 Oct-Dec;16(5-6):348-56. Epub 2006 Nov 2. PubMed PMID: 17084100.

99: Warzecha Z, Dembiński A, Ceranowicz P, Dembiński M, Cieszkowski J, Konturek SJ, Polus A, Pawlik WW, Kuwahara A, Kato I, Konturek PC. Influence of ghrelin on gastric and duodenal growth and expression of digestive enzymes in young mature rats. J Physiol Pharmacol. 2006 Sep;57(3):425-37. PubMed PMID: 17033095.

100: Nogueiras R, Pfluger P, Tovar S, Arnold M, Mitchell S, Morris A, Perez-Tilve D, Vázquez MJ, Wiedmer P, Castañeda TR, DiMarchi R, Tschöp M, Schurmann A, Joost HG, Williams LM, Langhans W, Diéguez C. Effects of obestatin on energy balance and growth hormone secretion in rodents. Endocrinology. 2007 Jan;148(1):21-6. Epub 2006 Sep 28. PubMed PMID: 17008393.

101: Gaddipati KV, Simonian HP, Kresge KM, Boden GH, Parkman HP. Abnormal ghrelin and pancreatic polypeptide responses in gastroparesis. Dig Dis Sci. 2006 Aug;51(8):1339-46. Epub 2006 Jul 26. PubMed PMID: 16868831.

102: Brzozowski T, Konturek PC, Sliwowski Z, Pajdo R, Drozdowicz D, Kwiecien S, Burnat G, Konturek SJ, Pawlik WW. Prostaglandin/cyclooxygenase pathway in ghrelin-induced gastroprotection against ischemia-reperfusion injury. J Pharmacol Exp Ther. 2006 Oct;319(1):477-87. Epub 2006 Jul 25. PubMed PMID: 16868036.

103: Yakabi K, Ro S, Onouhi T, Tanaka T, Ohno S, Miura S, Johno Y, Takayama K. Histamine mediates the stimulatory action of ghrelin on acid secretion in rat stomach. Dig Dis Sci. 2006 Aug;51(8):1313-21. Epub 2006 Jul 13. PubMed PMID: 16838121.

104: Pekic S, Pesko P, Djurovic M, Miljic D, Doknic M, Glodic J, Dieguez C, Casanueva FF, Popovic V. Plasma ghrelin levels of gastrectomized and vagotomized patients are not affected by glucose administration. Clin Endocrinol (Oxf). 2006 Jun;64(6):684-8. PubMed PMID: 16712672.

105: Wasko R, Jaskula M, Komarowska H, Zamyslowska H, Sowinski J, Waligorska-Stachura J. Ghrelin concentrations in acromegalic patients in relation to the administered therapy. Neuro Endocrinol Lett. 2006 Feb-Apr;27(1-2):162-8. PubMed PMID: 16670671.

106: Nagamine J, Kawamura T, Tokunaga T, Hume WE, Nagata R, Nakagawa T, Taiji M. Synthesis and pharmacological profile of an orally-active growth hormone secretagogue, SM-130686. Comb Chem High Throughput Screen. 2006 Mar;9(3):187-96. Review. PubMed PMID: 16533152.

107: Brzozowski T, Konturek PC, Drozdowicz D, Konturek SJ, Pawlik M, Sliwowski Z, Pawlik WW, Hahn EG. Role of central and peripheral ghrelin in the mechanism of gastric mucosal defence. Inflammopharmacology. 2005;13(1-3):45-62. PubMed PMID: 16259727.

108: Chen CY, Inui A, Asakawa A, Fujino K, Kato I, Chen CC, Ueno N, Fujimiya M. Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats. Gastroenterology. 2005 Jul;129(1):8-25. PubMed PMID: 16012930.

109: Xu XB, Pang JJ, Cao JM, Ni C, Xu RK, Peng XZ, Yu XX, Guo S, Chen MC, Chen C. GH-releasing peptides improve cardiac dysfunction and cachexia and suppress stress-related hormones and cardiomyocyte apoptosis in rats with heart failure. Am J Physiol Heart Circ Physiol. 2005 Oct;289(4):H1643-51. Epub 2005 Jun 10. PubMed PMID: 15951341.

110: le Roux CW, Neary NM, Halsey TJ, Small CJ, Martinez-Isla AM, Ghatei MA, Theodorou NA, Bloom SR. Ghrelin does not stimulate food intake in patients with surgical procedures involving vagotomy. J Clin Endocrinol Metab. 2005 Aug;90(8):4521-4. Epub 2005 May 24. PubMed PMID: 15914532.

111: Abbott CR, Monteiro M, Small CJ, Sajedi A, Smith KL, Parkinson JR, Ghatei MA, Bloom SR. The inhibitory effects of peripheral administration of peptide YY(3-36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway. Brain Res. 2005 May 17;1044(1):127-31. Epub 2005 Apr 7. PubMed PMID: 15862798.

112: Koda S, Date Y, Murakami N, Shimbara T, Hanada T, Toshinai K, Niijima A, Furuya M, Inomata N, Osuye K, Nakazato M. The role of the vagal nerve in peripheral PYY3-36-induced feeding reduction in rats. Endocrinology. 2005 May;146(5):2369-75. Epub 2005 Feb 17. PubMed PMID: 15718279.

113: Libè R, Morpurgo PS, Cappiello V, Maffini A, Bondioni S, Locatelli M, Zavanone M, Beck-Peccoz P, Spada A. Ghrelin and adiponectin in patients with Cushing's disease before and after successful transsphenoidal surgery. Clin Endocrinol (Oxf). 2005 Jan;62(1):30-6. PubMed PMID: 15638867.

114: Takeno R, Okimura Y, Iguchi G, Kishimoto M, Kudo T, Takahashi K, Takahashi Y, Kaji H, Ohno M, Ikuta H, Kuroda Y, Obara T, Hosoda H, Kangawa K, Chihara K. Intravenous administration of ghrelin stimulates growth hormone secretion in vagotomized patients as well as normal subjects. Eur J Endocrinol. 2004 Oct;151(4):447-50. PubMed PMID: 15476443.

115: Brzozowski T, Konturek PC, Konturek SJ, Kwiecień S, Drozdowicz D, Bielanski W, Pajdo R, Ptak A, Nikiforuk A, Pawlik WW, Hahn EG. Exogenous and endogenous ghrelin in gastroprotection against stress-induced gastric damage. Regul Pept. 2004 Aug 15;120(1-3):39-51. PubMed PMID: 15177919.

116: Zhang W, Lin TR, Hu Y, Fan Y, Zhao L, Mulholland MW. Activation of c-fos expression in the rat inferior olivary nucleus by ghrelin. Neurosci Lett. 2003 Dec 26;353(3):157-60. PubMed PMID: 14665405.

117: Kim K, Sanno N, Arai K, Takano K, Yasufuku-Takano J, Teramoto A, Shibasaki T. Ghrelin mRNA and GH secretagogue receptor mRNA in human GH-producing pituitary adenomas is affected by mutations in the alpha subunit of G protein. Clin Endocrinol (Oxf). 2003 Nov;59(5):630-6. PubMed PMID: 14616888.

118: Williams DL, Grill HJ, Cummings DE, Kaplan JM. Vagotomy dissociates short- and long-term controls of circulating ghrelin. Endocrinology. 2003 Dec;144(12):5184-7. Epub 2003 Oct 2. PubMed PMID: 14525914.

119: Fujino K, Inui A, Asakawa A, Kihara N, Fujimura M, Fujimiya M. Ghrelin induces fasted motor activity of the gastrointestinal tract in conscious fed rats. J Physiol. 2003 Jul 1;550(Pt 1):227-40. PubMed PMID: 12837928; PubMed Central PMCID: PMC2343006.

120: Torsello A, Bresciani E, Rossoni G, Avallone R, Tulipano G, Cocchi D, Bulgarelli I, Deghenghi R, Berti F, Locatelli V. Ghrelin plays a minor role in the physiological control of cardiac function in the rat. Endocrinology. 2003 May;144(5):1787-92. PubMed PMID: 12697684.

121: Sibilia V, Rindi G, Pagani F, Rapetti D, Locatelli V, Torsello A, Campanini N, Deghenghi R, Netti C. Ghrelin protects against ethanol-induced gastric ulcers in rats: studies on the mechanisms of action. Endocrinology. 2003 Jan;144(1):353-9. PubMed PMID: 12488364.

122: Barreiro ML, Gaytán F, Caminos JE, Pinilla L, Casanueva FF, Aguilar E, Diéguez C, Tena-Sempere M. Cellular location and hormonal regulation of ghrelin expression in rat testis. Biol Reprod. 2002 Dec;67(6):1768-76. PubMed PMID: 12444052.

123: Tschöp M, Flora DB, Mayer JP, Heiman ML. Hypophysectomy prevents ghrelin-induced adiposity and increases gastric ghrelin secretion in rats. Obes Res. 2002 Oct;10(10):991-9. PubMed PMID: 12376579.

124: Date Y, Murakami N, Toshinai K, Matsukura S, Niijima A, Matsuo H, Kangawa K, Nakazato M. The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology. 2002 Oct;123(4):1120-8. PubMed PMID: 12360474.

125: Lee HM, Wang G, Englander EW, Kojima M, Greeley GH Jr. Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology. 2002 Jan;143(1):185-90. PubMed PMID: 11751608.

126: Zhang W, Chen M, Chen X, Segura BJ, Mulholland MW. Inhibition of pancreatic protein secretion by ghrelin in the rat. J Physiol. 2001 Nov 15;537(Pt 1):231-6. PubMed PMID: 11711576; PubMed Central PMCID: PMC2278918.

127: Date Y, Nakazato M, Murakami N, Kojima M, Kangawa K, Matsukura S. Ghrelin acts in the central nervous system to stimulate gastric acid secretion. Biochem Biophys Res Commun. 2001 Jan 26;280(3):904-7. PubMed PMID: 11162609.

128: Masuda Y, Tanaka T, Inomata N, Ohnuma N, Tanaka S, Itoh Z, Hosoda H, Kojima M, Kangawa K. Ghrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun. 2000 Oct 5;276(3):905-8. PubMed PMID: 11027567.

129: Adams EF, Huang B, Buchfelder M, Howard A, Smith RG, Feighner SD, van der Ploeg LH, Bowers CY, Fahlbusch R. Presence of growth hormone secretagogue receptor messenger ribonucleic acid in human pituitary tumors and rat GH3 cells. J Clin Endocrinol Metab. 1998 Feb;83(2):638-42. PubMed PMID: 9467586.