Tachykinin peptides

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Tachykinin family
Identifiers
Symbol Tachykinin
Pfam PF02202
InterPro IPR002040
SMART TK
PROSITE PDOC00240
SCOP 1myu
OPM family 152
OPM protein 1myu
Available PDB structures:

1myuA:3-12 1n6tA:1-10

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.

Contents

[edit] 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,[8][9] while NK2 antagonists have been proposed as anxiolytics[10][11] and NK3 antagonists have been proposed as antipsychotics.[12][13]

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.[14][15][16] The main use for which these drugs have been applied so far however is as antiemetics, in both human and veterinary medicine.[17][18]

Examples of tachykinin antagonists include;[19]

[edit] Subfamilies

[edit] References

  1. ^ a b PMID 1695945
  2. ^ Maggio JE (1988). "Tachykinins". Annu. Rev. Neurosci. 11: 13–28. doi:10.1146/annurev.ne.11.030188.000305. PMID 3284438. 
  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. PMID 1969374. 
  4. ^ Avanov AIa (1992). "Tachykinins and conformational aspects of their interactions with receptors". Mol. Biol. (Mosk) 26 (1): 5–24. PMID 1324401. 
  5. ^ PMID 7690487
  6. ^ OMIM:TAC1.
  7. ^ OMIM:TAC3.
  8. ^ Alvaro G, Di Fabio R. Neurokinin 1 receptor antagonists - current prospects. Current Opinion in Drug Discovery and Development. 2007 Sep;10(5):613-21. PMID 17786860
  9. ^ Duffy RA. Potential therapeutic targets for neurokinin-1 receptor antagonists. Expert Opinion on Emerging Drugs. 2004 May;9(1):9-21. PMID 15155133
  10. ^ Salomé N, Stemmelin J, Cohen C, Griebel G. Selective blockade of NK2 or NK3 receptors produces anxiolytic- and antidepressant-like effects in gerbils. Pharmacology, Biochemistry and Behaviour. 2006 Apr;83(4):533-9. PMID 16624395
  11. ^ Louis C, Stemmelin J, Boulay D, Bergis O, Cohen C, Griebel G. Additional evidence for anxiolytic- and antidepressant-like activities of saredutant (SR48968), an antagonist at the neurokinin-2 receptor in various rodent-models. Pharmacology, Biochemistry and Behaviour. 2008 Mar;89(1):36-45. PMID 18045668
  12. ^ Spooren W, Riemer C, Meltzer H. Opinion: NK3 receptor antagonists: the next generation of antipsychotics? Nature Reviews. Drug Discovery. 2005 Dec;4(12):967-75. PMID 16341062
  13. ^ Chahl LA. Tachykinins and neuropsychiatric disorders. Current Drug Targets. 2006 Aug;7(8):993-1003. PMID 16918327
  14. ^ Groneberg DA, Harrison S, Dinh QT, Geppetti P, Fischer A. Tachykinins in the respiratory tract. Current Drug Targets. 2006 Aug;7(8):1005-10. PMID 16918328
  15. ^ Improta G, Broccardo M. Tachykinins: role in human gastrointestinal tract physiology and pathology. Current Drug Targets. 2006 Aug;7(8):1021-9. PMID 16918330
  16. ^ Boot JD, de Haas S, Tarasevych S, Roy C, Wang L, Amin D, Cohen J, Sterk PJ, Miller B, Paccaly A, Burggraaf J, Cohen AF, Diamant Z. Effect of an NK1/NK2 receptor antagonist on airway responses and inflammation to allergen in asthma. American Journal of Respiratory and Critical Care Medicine. 2007 Mar 1;175(5):450-7. PMID 17170385
  17. ^ Navari RM. Fosaprepitant (MK-0517): a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Expert Opinion on Investigational Drugs. 2007 Dec;16(12):1977-85. PMID 18042005
  18. ^ Hickman MA, Cox SR, Mahabir S, Miskell C, Lin J, Bunger A, McCall RB. Safety, pharmacokinetics and use of the novel NK-1 receptor antagonist maropitant (Cerenia) for the prevention of emesis and motion sickness in cats. Journal of Veterinary Pharmacology and Therapeutics. 2008 Jun;31(3):220-9. PMID 18471143
  19. ^ Quartara L, Altamura M. Tachykinin receptors antagonists: from research to clinic. Current Drug Targets. 2006 Aug;7(8):975-92. PMID 16918326

[edit] External links

v • d • e
Peptides: neuropeptides
Hypothalamic
Gastrointestinal hormones
Other hormones
Other
v • d • e
Autacoids: kinins
v • d • e
Kinins, neuropeptides: tachykinins
Mammal
Amphibian

This article includes text from the public domain Pfam and InterPro IPR002040

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