Neuropeptides are small protein-like molecules (peptides) used by neurons to communicate with each other. They are neuronal signaling molecules that influence the activity of the brain in specific ways. Different neuropeptides are involved in a wide range of brain functions, including analgesia, reward, food intake, metabolism, reproduction, social behaviors, learning, and memory.

Neuropeptides are related to peptide hormones, and in some cases, peptides that function in the periphery as hormones also have neuronal functions as neuropeptides. The distinction between neuropeptide and peptide hormone has to do with the cell types that release and respond to the molecule; neuropeptides are secreted from neuronal cells (primarily neurons but also glia for some peptides) and signal to neighbor cells (primarily neurons). In contrast, peptide hormones are secreted from neuroendocrine cells and travel through the blood to distant tissues where they evoke a response. Both neuropeptides and peptide hormones are synthesized by the same sets of enzymes, which include prohormone convertases and carboxypeptidases that selectively cleave the peptide precursor at specific processing sites to generate the bioactive peptides.

Neuropeptides modulate neuronal communication by acting on cell surface receptors. Many neuropeptides are co-released with other small-molecule neurotransmitters. The human genome contains about 90 genes that encode precursors of neuropeptides. At present, about 100 different peptides are known to be released by different populations of neurons in the mammalian brain.

Neurons use many different chemical signals to communicate information, including neurotransmitters, peptides, and gasotransmitters. Peptides are unique among these cell-cell signaling molecules in several respects. One major difference is that peptides are not recycled back into the cell once secreted, unlike many conventional neurotransmitters (glutamate, dopamine, serotonin). Another difference is that after secretion, peptides are modified by extracellular peptidases; in some cases, these extracellular cleavages inactivate the biological activity, but in other cases the extracellular cleavages increase the affinity of a peptide for a particular receptor while decreasing its affinity for another receptor. These extracellular processing events add to the complexity of neuropeptides as cell-cell signaling molecules.

Many populations of neurons have distinctive biochemical phenotypes. For example, in one subpopulation of about 3000 neurons in the arcuate nucleus of the hypothalamus, three anorectic peptides are co-expressed: α-melanocyte-stimulating hormone (α-MSH), galanin-like peptide, and cocaine-and-amphetamine-regulated transcript (CART), and in another subpopulation two orexigenic peptides are co-expressed, neuropeptide Y and agouti-related peptide (AGRP). These are not the only peptides in the arcuate nucleus; β-endorphin, dynorphin, enkephalin, galanin, ghrelin, growth-hormone-releasing hormone, neurotensin, neuromedin U, and somatostatin are also expressed in subpopulations of arcuate neurons. These peptides are all released centrally and act on other neurons at specific receptors. The neuropeptide Y neurons also make the classical inhibitory neurotransmitter GABA.

Invertebrates also have many neuropeptides. CCAP has several functions including regulating heart rate, allatostatin and proctolin regulate food intake and growth, bursicon controls tanning of the cuticle and corazonin has a role in cuticle pigmentation and moulting.

Peptide signals play a role in information processing that is different from that of conventional neurotransmitters, and many appear to be particularly associated with specific behaviours. For example, oxytocin and vasopressin have striking and specific effects on social behaviours, including maternal behavior and pair bonding.

A variety of neuropeptides play important roles as neurotransmitters or neurotransmitter modifiers in the brain, and may be involved in the incidence and development of epilepsy. In recent years, the following neuropeptides: galanin (GAL), neuropeptide Y (NPY), neuropeptide substance P (SP), cholecystokinin (CCK), as well as wake-promoting neuropeptide (ORE) have been discovered to be closely associated with epilepsy 1).

Gao JB, Bao M. Plasma neuropeptide as a prognostic marker of vagus nerve stimulation in the treatment of epilepsy. Brain Stimul. 2020 Apr 1;13(4):959-960. doi: 10.1016/j.brs.2020.03.021. [Epub ahead of print] PubMed PMID: 32380447.
  • neuropeptide.txt
  • Last modified: 2020/05/08 11:37
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