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Tachykinin peptides

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Tachykinin peptides are one of the largest family of neuropeptides, found from amphibians to mammals. They were so named due to their ability to rapidly induce contraction of gut tissue.[1] The tachykinin family is characterized by a common C-terminal sequence, Phe-X-Gly-Leu-Met-NH2, where X is either an Aromatic or an Aliphatic amino acid. The genes that produce tachykinins encode precursor proteins called preprotachykinins, which are chopped apart into smaller peptides by posttranslational proteolytic processing. The genes also code for multiple splice forms which are made up of different sets of peptides.

Tachykinins[2][3][4] excite neurons, evoke behavioral responses, are potent vasodilatators and contract (directly or indirectly) many smooth muscles. Tachykinins are from ten to twelve residues long.

The two human tachykinin genes are called TAC1 and TAC3 for historical reasons, and are equivalent to Tac1 and Tac2 of the mouse, respectively. TAC1 encodes neurokinin A (formerly known as substance K), neuropeptide K (which has also been called neurokinin K[5]), neuropeptide gamma, and substance P.[6] Alpha, beta, and gamma splice forms are produced; the alpha form lacks exon 6 and the gamma form lacks exon 4. All three splice forms of TAC1 produce substance P, but only the beta and gamma forms produce the other three peptides. Neuropeptide K and neuropeptide gamma are N-terminally longer versions of neurokinin A which appear to be final peptide products in some tissues.[1]

TAC3 encodes neurokinin B.[7]

The most notable tachykinin is Substance P.

Receptors

See main article at tachykinin receptor

There are three known mammalian tachykinin receptors termed NK1, NK2 and NK3. All are members of the 7 transmembrane g protein-coupled family of receptors and induce the activation of phospholipase C, producing inositol triphosphate. NK1, NK2 and NK3 selectively bind to substance P, neurokinin A and neurokinin B, respectively. Whilst the receptors are not specific to any individual tachykinin, they do have differing affinity for the tachykinins:

  • NK1: SP>NKA>NKB;
  • NK2: NKA>NKB>SP;
  • NK3: NKB>NKA>SP.

Antagonists of neurokinin-1 (NK(1)) receptors (NK1 receptor antagonists), through which substance P acts, have been proposed to belong to a new class of antidepressants.

Subfamilies

References

  1. 1.0 1.1 PMID 1695945
  2. Maggio JE (1988). Tachykinins. Annu. Rev. Neurosci. 11: 13-28.
  3. Helke CJ, Krause JE, Mantyh PW, Couture R, Bannon MJ (1990). Diversity in mammalian tachykinin peptidergic neurons: multiple peptides, receptors, and regulatory mechanisms. FASEB J. 4 (6): 1606-1615.
  4. Avanov AIa (1992). Tachykinins and conformational aspects of their interactions with receptors. Mol. Biol. (Mosk) 26 (1): 5-24.
  5. PMID 7690487
  6. OMIM:TAC1.
  7. OMIM:TAC3.

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