Tachykinin peptides
{{Pfam_box
| Symbol = Tachykinin
| Name = Tachykinin family
| image = PDB 1myu EBI.jpg
| width =
| caption = Structure of the tachykinin peptide Kassinin.{{cite journal |vauthors=Grace RC, Lynn AM, Cowsik SM |title=Lipid induced conformation of the tachykinin peptide Kassinin |journal=J. Biomol. Struct. Dyn. |volume=18 |issue=4 |pages=611–21, 623–5 |date=February 2001 |pmid=11245256 |doi= 10.1080/07391102.2001.10506693|s2cid=42266413 }}
| Pfam= PF02202
| InterPro= IPR002040
| SMART= TK
| PROSITE = PDOC00240
| SCOP = 1myu
| TCDB =
| OPM family=143
| OPM protein= 1myu
| PDB=
}}
Tachykinin peptides are one of the largest families of neuropeptides, found from amphibians to mammals. They were so named due to their ability to rapidly induce contraction of gut tissue.{{cite journal |vauthors=Carter MS, Krause JE |title=Structure, expression, and some regulatory mechanisms of the rat preprotachykinin gene encoding substance P, neurokinin A, neuropeptide K, and neuropeptide gamma |journal=J. Neurosci. |volume=10 |issue=7 |pages=2203–14 |date=July 1990 |pmid=1695945 |doi= 10.1523/JNEUROSCI.10-07-02203.1990|doi-access=free |pmc=6570392 }} 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 that are made up of different sets of peptides.
Tachykinins{{cite journal |author=Maggio JE |title=Tachykinins |journal=Annu. Rev. Neurosci. |volume=11 |pages=13–28 |year=1988 |pmid=3284438 |doi=10.1146/annurev.ne.11.030188.000305}}{{cite journal |vauthors=Helke CJ, Krause JE, Mantyh PW, Couture R, Bannon MJ |title=Diversity in mammalian tachykinin peptidergic neurons: multiple peptides, receptors, and regulatory mechanisms |journal=FASEB J. |volume=4 |issue=6 |pages=1606–15 |year=1990 |pmid=1969374|doi=10.1096/fasebj.4.6.1969374 |doi-access=free |s2cid=25935155 }}{{cite journal |author=Avanov AIa |title=Tachykinins and conformational aspects of their interactions with receptors |journal=Mol. Biol. (Mosk) |volume=26 |issue=1 |pages=5–24 |year=1992 |pmid=1324401}} 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{{cite journal |vauthors=Dornan WA, Vink KL, Malen P, Short K, Struthers W, Barrett C |title=Site-specific effects of intracerebral injections of three neurokinins (neurokinin A, neurokinin K, and neurokinin gamma) on the expression of male rat sexual behavior |journal=Physiol. Behav. |volume=54 |issue=2 |pages=249–58 |date=August 1993 |pmid=7690487 |doi= 10.1016/0031-9384(93)90107-Q|s2cid=33412235 }}), neuropeptide gamma, and Substance P.{{OMIM|162320|TAC1}} 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 that appear to be final peptide products in some tissues.
TAC3 encodes neurokinin B.{{OMIM|162330|TAC3}}
The best known tachykinin is Substance P.
Receptors
{{main|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,{{cite journal
|vauthors=Alvaro G, Di Fabio R |title=Neurokinin 1 receptor antagonists--current prospects |journal=Curr Opin Drug Discov Dev |volume=10 |issue=5 |pages=613–21 |date=September 2007 |pmid=17786860 }}
{{cite journal |author=Duffy RA |title=Potential therapeutic targets for neurokinin-1 receptor antagonists |journal=Expert Opin Emerg Drugs |volume=9 |issue=1 |pages=9–21 |date=May 2004 |pmid=15155133 |doi=10.1517/eoed.9.1.9.32956 }} while NK2 antagonists have been proposed as anxiolytics{{cite journal |vauthors=Salomé N, Stemmelin J, Cohen C, Griebel G |title=Selective blockade of NK2 or NK3 receptors produces anxiolytic- and antidepressant-like effects in gerbils |journal=Pharmacol. Biochem. Behav. |volume=83 |issue=4 |pages=533–9 |date=April 2006 |pmid=16624395 |doi=10.1016/j.pbb.2006.03.013 |s2cid=15134994 }}{{cite journal |vauthors=Louis C, Stemmelin J, Boulay D, Bergis O, Cohen C, Griebel G |title=Additional evidence for anxiolytic- and antidepressant-like activities of saredutant (SR48968), an antagonist at the neurokinin-2 receptor in various rodent-models |journal=Pharmacol. Biochem. Behav. |volume=89 |issue=1 |pages=36–45 |date=March 2008 |pmid=18045668 |doi=10.1016/j.pbb.2007.10.020 |s2cid=21490514 }} and NK3 antagonists have been proposed as antipsychotics.{{cite journal
|vauthors=Spooren W, Riemer C, Meltzer H |title=Opinion: NK3 receptor antagonists: the next generation of antipsychotics? |journal=Nat Rev Drug Discov |volume=4 |issue=12 |pages=967–75 |date=December 2005 |pmid=16341062 |doi=10.1038/nrd1905 |s2cid=13270787 }}
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.{{cite journal
|vauthors=Groneberg DA, Harrison S, Dinh QT, Geppetti P, Fischer A |title=Tachykinins in the respiratory tract |journal=Curr Drug Targets |volume=7 |issue=8 |pages=1005–10 |date=August 2006 |pmid=16918328 |doi= 10.2174/138945006778019318|url=http://www.bentham-direct.org/pages/content.php?CDT/2006/00000007/00000008/0009J.SGM|archive-url=https://archive.today/20120801221258/http://www.bentham-direct.org/pages/content.php?CDT/2006/00000007/00000008/0009J.SGM|url-status=usurped|archive-date=August 1, 2012}}
{{cite journal |vauthors=Boot JD, de Haas S, Tarasevych S, etal |title=Effect of an NK1/NK2 receptor antagonist on airway responses and inflammation to allergen in asthma |journal=Am. J. Respir. Crit. Care Med. |volume=175 |issue=5 |pages=450–7 |date=March 2007 |pmid=17170385 |doi=10.1164/rccm.200608-1186OC |s2cid=22707433 }} The main use for which these antagonist drugs have been applied so far, however, is as antiemetics, in both human and veterinary medicine.{{cite journal
|author=Navari RM |title=Fosaprepitant (MK-0517): a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting |journal=Expert Opin Investig Drugs |volume=16 |issue=12 |pages=1977–85 |date=December 2007 |pmid=18042005 |doi=10.1517/13543784.16.12.1977 |s2cid=21437603 }}
Subfamilies
- Tachykinin {{InterPro|IPR008215}}
References
{{reflist|2}}
External links
- {{MeshName|Tachykinins}}
{{Neuropeptides}}
{{Autacoids}}
{{InterPro content|IPR002040}}