Peptide Neurotransmitters and Hormones

Abstract

Neuropeptides are a structurally diverse class of chemical messengers that play important roles in the coordination of many physiological and behavioural events. Neuropeptides are derived from the cleavage of larger precursor proteins at the dibasic amino acid sites by prohormone convertases. They are synthesised in the cell body, packaged in the large dense core vesicles and released in a neuronal activity‐dependent manner. The neuropeptides may function as blood‐borne hormones or as mediators/transmitters affecting neuronal activity in the nervous system. In the target cells, neuropeptides activate the complementary G protein‐coupled receptors and elicit responses that are specific to these cells. The released peptide is subsequently inactivated by the actions of several nonspecific extracellular peptidases. Key Concepts Neuropeptides are a structurally diverse class of chemical messengers produced by nerve cells to coordinate many physiological and behavioural processes. The major neuroendocrine centre in the brain is the pituitary gland. Neuropeptides are derived from the cleavage of the larger precursor proteins by specific endoproteases that are copackaged in the dense core secretory granules. Receptors for neuropeptides belong mainly to the family of G protein‐coupled receptor. G protein‐coupled receptor may be activated in complex modes beyond their interaction with G proteins.

Modified synthetic peptides: from therapeutics to chemosensors

“…Peptides are frequently involved in human physiology, acting as hormones, 7 neurotransmitters, 8 growth factors, 9 or ion channel ligands. 10 Moreover, peptides tend to act as intrinsic signalling molecules for many of these physiological functions, opening up the possibility for peptide-therapeutic mediation that closely resembles the natural process.…”

“…67 The introduction of these structurally diverse amino acids into the peptide sequenceeven more so at the site of proteolysiscan be an effective method for increasing the plasma half-life of peptide therapeutics. An interesting example is selepressinan analogue of vasopressin, containing the backbone modification [Phe (2) , Ile (3) , Hgn (4) , Orn(iPr) (8) ]which was being developed by Ferring Pharmaceuticals for the treatment of vasodilatory hypotension in septic shock. 68 Selepressin seen early clinical success, displaying comparable selectivity coupled with an enhanced plasma half-life.…”