Tachykinin peptides

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Tachykinin family
File:PDB 1myu EBI.jpg
Structure of the tachykinin peptide Kassinin.[1]
Identifiers
SymbolTachykinin
PfamPF02202
InterProIPR002040
SMARTTK
PROSITEPDOC00240
SCOP1myu
SUPERFAMILY1myu
OPM superfamily152
OPM protein1myu

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.[2] 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[3][4][5] excite neurons, evoke behavioral responses, are potent vasodilators 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[6]), neuropeptide gamma, and substance P.[7] 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.[2]

TAC3 encodes neurokinin B.[8]

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 (NK1) receptors (NK1 receptor antagonists), through which substance P acts, have been proposed to belong to a new class of antidepressants,[9] [10] while NK2 antagonists have been proposed as anxiolytics[11][12] and NK3 antagonists have been proposed as antipsychotics.[13] [14]

Tachykinin peptides are also involved in inflammation, and tachykinin receptor antagonists have been researched for use in treating inflammatory conditions such as asthma and irritable bowel syndrome.[15] [16] [17] The main use for which these drugs have been applied so far however is as antiemetics, in both human and veterinary medicine.[18] [19]

Examples of tachykinin antagonists include;[20]

Subfamilies

References

  1. Grace RC, Lynn AM, Cowsik SM (2001). "Lipid induced conformation of the tachykinin peptide Kassinin". J. Biomol. Struct. Dyn. 18 (4): 611–21, 623–5. PMID 11245256. Unknown parameter |month= ignored (help)
  2. 2.0 2.1 Carter MS, Krause JE (1990). "Structure, expression, and some regulatory mechanisms of the rat preprotachykinin gene encoding substance P, neurokinin A, neuropeptide K, and neuropeptide gamma". J. Neurosci. 10 (7): 2203–14. PMID 1695945. Unknown parameter |month= ignored (help)
  3. Maggio JE (1988). "Tachykinins". Annu. Rev. Neurosci. 11: 13–28. doi:10.1146/annurev.ne.11.030188.000305. PMID 3284438.
  4. 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): 1606–15. PMID 1969374.
  5. Avanov AIa (1992). "Tachykinins and conformational aspects of their interactions with receptors". Mol. Biol. (Mosk). 26 (1): 5–24. PMID 1324401.
  6. Dornan WA, Vink KL, Malen P, Short K, Struthers W, Barrett C (1993). "Site-specific effects of intracerebral injections of three neurokinins (neurokinin A, neurokinin K, and neurokinin gamma) on the expression of male rat sexual behavior". Physiol. Behav. 54 (2): 249–58. doi:10.1016/0031-9384(93)90107-Q. PMID 7690487. Unknown parameter |month= ignored (help)
  7. Online Mendelian Inheritance in Man (OMIM) TAC1 -162320
  8. Online Mendelian Inheritance in Man (OMIM) TAC3 -162330
  9. Alvaro G, Di Fabio R (2007). "Neurokinin 1 receptor antagonists--current prospects". Curr Opin Drug Discov Devel. 10 (5): 613–21. PMID 17786860. Unknown parameter |month= ignored (help)
  10. Duffy RA (2004). "Potential therapeutic targets for neurokinin-1 receptor antagonists". Expert Opin Emerg Drugs. 9 (1): 9–21. doi:10.1517/eoed.9.1.9.32956. PMID 15155133. Unknown parameter |month= ignored (help)
  11. Salomé N, Stemmelin J, Cohen C, Griebel G (2006). "Selective blockade of NK2 or NK3 receptors produces anxiolytic- and antidepressant-like effects in gerbils". Pharmacol. Biochem. Behav. 83 (4): 533–9. doi:10.1016/j.pbb.2006.03.013. PMID 16624395. Unknown parameter |month= ignored (help)
  12. Louis C, Stemmelin J, Boulay D, Bergis O, Cohen C, Griebel G (2008). "Additional evidence for anxiolytic- and antidepressant-like activities of saredutant (SR48968), an antagonist at the neurokinin-2 receptor in various rodent-models". Pharmacol. Biochem. Behav. 89 (1): 36–45. doi:10.1016/j.pbb.2007.10.020. PMID 18045668. Unknown parameter |month= ignored (help)
  13. Spooren W, Riemer C, Meltzer H (2005). "Opinion: NK3 receptor antagonists: the next generation of antipsychotics?". Nat Rev Drug Discov. 4 (12): 967–75. doi:10.1038/nrd1905. PMID 16341062. Unknown parameter |month= ignored (help)
  14. Chahl LA (2006). "Tachykinins and neuropsychiatric disorders". Curr Drug Targets. 7 (8): 993–1003. doi:10.2174/138945006778019309. PMID 16918327. Unknown parameter |month= ignored (help)
  15. Groneberg DA, Harrison S, Dinh QT, Geppetti P, Fischer A (2006). "Tachykinins in the respiratory tract". Curr Drug Targets. 7 (8): 1005–10. doi:10.2174/138945006778019318. PMID 16918328. Unknown parameter |month= ignored (help)
  16. Improta G, Broccardo M (2006). "Tachykinins: role in human gastrointestinal tract physiology and pathology". Curr Drug Targets. 7 (8): 1021–9. doi:10.2174/138945006778019354. PMID 16918330. Unknown parameter |month= ignored (help)
  17. Boot JD, de Haas S, Tarasevych S; et al. (2007). "Effect of an NK1/NK2 receptor antagonist on airway responses and inflammation to allergen in asthma". Am. J. Respir. Crit. Care Med. 175 (5): 450–7. doi:10.1164/rccm.200608-1186OC. PMID 17170385. Unknown parameter |month= ignored (help)
  18. Navari RM (2007). "Fosaprepitant (MK-0517): a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting". Expert Opin Investig Drugs. 16 (12): 1977–85. doi:10.1517/13543784.16.12.1977. PMID 18042005. Unknown parameter |month= ignored (help)
  19. Hickman MA, Cox SR, Mahabir S; et al. (2008). "Safety, pharmacokinetics and use of the novel NK-1 receptor antagonist maropitant (Cerenia) for the prevention of emesis and motion sickness in cats". J. Vet. Pharmacol. Ther. 31 (3): 220–9. doi:10.1111/j.1365-2885.2008.00952.x. PMID 18471143. Unknown parameter |month= ignored (help)
  20. Quartara L, Altamura M (2006). "Tachykinin receptors antagonists: from research to clinic". Curr Drug Targets. 7 (8): 975–92. doi:10.2174/138945006778019381. PMID 16918326. Unknown parameter |month= ignored (help)

External links

This article incorporates text from the public domain Pfam and InterPro: IPR002040

it:Tachichinina