Tachykinin, CGRP and their receptors

Substance P(SP), a major peptide neurotransmitter, was first found in the gut, and after two decades from its discovery it was proposed as a mediator of pain at the spinal level. SP belongs to the tachykinin, a family of peptides that share a common C-terminus amino-acid sequence (Phe–X–Gly–Leu– Met–NH2). In mammals the tachykinin are substantially confined to the central and peripheral nervous system. Three main tachykinin peptides have been described: SP, neurokinin A(NKA) and neurokinin B(NKB). SP and NKA are products of the preprotachykinin gene-I that via alternative splicing of the mRNA generates three different precursor proteins from which SP and NKA are produced at different ratios. The sole biologically active product of the preprotachykinin gene-II is NKB. NKB expression is apparently limited to the central nervous system, whereas SP and NKA are also found in a subpopulation of intrinsic neurones of the gut and in a subset of primary sensory neurones, including those of the trigeminal and dorsal root ganglia. Of particular interest for this review is the notion that vagal (nodose and jugular) sensory ganglia are made up of a large proportion of neurones that contain and release tachykinin. Metabolism by membrane-bound peptidases, including neutral endopeptidase (NEP, EC 24.11) and angiotensin converting enzyme (ACE, EC 14.1), is one of the major factors that limit the biological effects of tachykinin.