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Tachykinin peptides

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(Redirected fromNeurokinin)
Tachykinin family
Structure of the tachykinin peptide Kassinin.[1]
Identifiers
SymbolTachykinin
PfamPF02202
InterProIPR002040
SMARTTK
PROSITEPDOC00240
SCOP21myu/SCOPe/SUPFAM
OPM superfamily143
OPM protein1myu
Available protein structures:
Pfam structures/ECOD
PDBRCSB PDB;PDBe;PDBj
PDBsumstructure summary

Tachykinin peptidesare one of the largest families ofneuropeptides,found fromamphibianstomammals.They were so named due to their ability to rapidly induce contraction of gut tissue.[2]The tachykinin family is characterized by a commonC-terminalsequence,Phe-X-Gly-Leu-Met-NH2, where X is either anAromaticor anAliphaticamino acid.Thegenesthat produce tachykinins encode precursor proteins calledpreprotachykinins,which are chopped apart into smallerpeptidesbyposttranslationalproteolyticprocessing. The genes also code for multiplesplice formsthat are made up of different sets of peptides.

Tachykinins[3][4][5]excite neurons, evoke behavioral responses, are potentvasodilators,and contract (directly or indirectly) many smooth muscles. Tachykinins are from ten to twelve residues long.

The two human tachykinin genes are calledTAC1andTAC3for historical reasons, and are equivalent to Tac1 and Tac2 of the mouse, respectively. TAC1 encodesneurokinin A(formerly known as substance K),neuropeptide K(which has also been called neurokinin K[6]),neuropeptide gamma,andSubstance P.[7]Alpha, beta, and gamma splice forms are produced; the alpha form lacksexon6 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 areN-terminallylonger versions of neurokinin A that appear to be final peptide products in some tissues.[2]

TAC3 encodesneurokinin B.[8]

The best known tachykinin isSubstance P.

Receptors

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Main article:Tachykinin receptor

There are three knownmammaliantachykininreceptors termed NK1,NK2and NK3.All are members of the7 transmembraneg protein-coupledfamily of receptors and induce the activation ofphospholipase C,producinginositol triphosphate.NK1,NK2and NK3selectively bind tosubstance P,neurokinin A,andneurokinin 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 ofantidepressants,[9] [10]while NK2antagonists have been proposed asanxiolytics[11][12]and NK3antagonists have been proposed asantipsychotics.[13] [14]

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

Examples of tachykinin antagonists include:[20]

Subfamilies

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References

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  1. ^Grace RC, Lynn AM, Cowsik SM (February 2001). "Lipid induced conformation of the tachykinin peptide Kassinin".J. Biomol. Struct. Dyn.18(4): 611–21, 623–5.doi:10.1080/07391102.2001.10506693.PMID11245256.S2CID42266413.
  2. ^abCarter MS, Krause JE (July 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.doi:10.1523/JNEUROSCI.10-07-02203.1990.PMC6570392.PMID1695945.
  3. ^Maggio JE (1988). "Tachykinins".Annu. Rev. Neurosci.11:13–28.doi:10.1146/annurev.ne.11.030188.000305.PMID3284438.
  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.doi:10.1096/fasebj.4.6.1969374.PMID1969374.S2CID25935155.
  5. ^Avanov AIa (1992). "Tachykinins and conformational aspects of their interactions with receptors".Mol. Biol. (Mosk).26(1): 5–24.PMID1324401.
  6. ^Dornan WA, Vink KL, Malen P, Short K, Struthers W, Barrett C (August 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.PMID7690487.S2CID33412235.
  7. ^Online Mendelian Inheritance in Man(OMIM):TAC1 - 162320
  8. ^Online Mendelian Inheritance in Man(OMIM):TAC3 - 162330
  9. ^Alvaro G, Di Fabio R (September 2007). "Neurokinin 1 receptor antagonists--current prospects".Curr Opin Drug Discov Dev.10(5): 613–21.PMID17786860.
  10. ^Duffy RA (May 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.PMID15155133.
  11. ^Salomé N, Stemmelin J, Cohen C, Griebel G (April 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.PMID16624395.S2CID15134994.
  12. ^Louis C, Stemmelin J, Boulay D, Bergis O, Cohen C, Griebel G (March 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.PMID18045668.S2CID21490514.
  13. ^Spooren W, Riemer C, Meltzer H (December 2005). "Opinion: NK3 receptor antagonists: the next generation of antipsychotics?".Nat Rev Drug Discov.4(12): 967–75.doi:10.1038/nrd1905.PMID16341062.S2CID13270787.
  14. ^Chahl LA (August 2006)."Tachykinins and neuropsychiatric disorders".Curr Drug Targets.7(8): 993–1003.doi:10.2174/138945006778019309.PMID16918327.
  15. ^Groneberg DA, Harrison S, Dinh QT, Geppetti P, Fischer A (August 2006)."Tachykinins in the respiratory tract".Curr Drug Targets.7(8): 1005–10.doi:10.2174/138945006778019318.PMID16918328.
  16. ^Improta G, Broccardo M (August 2006)."Tachykinins: role in human gastrointestinal tract physiology and pathology".Curr Drug Targets.7(8): 1021–9.doi:10.2174/138945006778019354.PMID16918330.
  17. ^Boot JD, de Haas S, Tarasevych S, et al. (March 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.PMID17170385.S2CID22707433.
  18. ^Navari RM (December 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.PMID18042005.S2CID21437603.
  19. ^Hickman MA, Cox SR, Mahabir S, et al. (June 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.PMID18471143.
  20. ^Quartara L, Altamura M (August 2006)."Tachykinin receptors antagonists: from research to clinic".Curr Drug Targets.7(8): 975–92.doi:10.2174/138945006778019381.PMID16918326.
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This article incorporates text from the public domainPfamandInterPro:IPR002040
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