Tahikinin

Tahikininska familija
	Struktura tahikininskog peptida kasinina.
Identifikatori
Simbol	Tahikinin
Pfam	PF02202
InterPro	IPR002040
SMART	TK
PROSITE	PDOC00240
SCOP	1myu
Superfamilija	1myu
OPM protein	152
OPM protein	1myu
Dostupne PDB strukture:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	strukturni pregled

Tahikininski peptidi su jedna od najvećih familija neuropeptida, nađenih kod vodozemaca i sisara. Tahikinini imaju od deset do dvanaest aminikiselinskih ostataka. Oni su dobili ime po njihovoj sposobnosti da brzo indukuju kontrakciju tkiva stomaka.^[2] Tahikininska familija je karakterisana zajedničkom sekvencom C-terminusa, Phe-X-Gly-Leu-Met-NH2, gde je X bilo aromatična ili alifatična aminokiselina. Geni koji proizvode tahikinine kodiraju prekursorske proteine zvane preprotahikinini, koji se presecaju u manje peptide posttranslaciono putem proteolitičkih transformacija. Ti geni takođe kodiraju više splajsnih formi.

Kratke činjenice Identifikatori, Simbol ...

Zatvori

Tahikinini^[3]^[4]^[5] pobuđuju neurone, i evociraju promene ponašanja. Oni su potentni vazodilatatori, i izazivaju kontrakcije mnogih glatkih mišića (direktno ili indirektno).

Ljudski tahikininski geni su TAC1 i TAC3. Ekvivalentni mišji geni su Tac1 i Tac2. TAC1 kodira neurokinin A (ranije poznat kao supstanca K), neuropeptid K (neurokinin K^[6]), neuropeptid gama, i supstancu P.^[7] Alfa, beta, i gama splajsne varijante se izražavaju. Alfa formi nedostaje ekson 6, a gama formi ekson 4. Sve tri splajsne forme TAC1 proteina proizvode supstancu P, a samo beta i gama forme proizvode druga tri peptida. Neuropeptid K i neuropeptid gama su N-terminalno duže verzije neurokinina A koji je finalni peptid u nekim tkivima.^[2] TAC3 kodira neurokinin B.^[8] Najpoznatiji tahikinin je supstanca P.

Glavni članak: Tahikininski receptor

Kod sisara su poznata tri tahikininska receptora: NK₁, NK₂ i NK₃. Svi članovi familije su 7-transmembranski G protein spregnuti receptori, koji indukuju aktivaciju fosfolipaze C, i proizvode inozitol trifosfat. NK₁, NK₂ i NK₃ selektivno vezuju supstancu P, neurokinin A i neurokinin B, respektivno. Ovi receptori nisu potpuno specifični za individualne tahikinine, već imaju različite afinitete:

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

Za antagoniste neurokinin-1 (NK₁) receptora je predloženo da pripadaju novoj klasi antidepresanata^[9]^[10], dok je za NK₂ antagoniste predloženo da su anksiolitici^[11]^[12], a NK₃ antagonisti su svrstani u antipsihotike.^[13]^[14]

Tahikininski peptidi takođe učestvuju u inflamaciji, i antagonisti tahikininskih receptora su istraživani za upotrebu u lečenju inflamatornih oboljenja kao što je astma i upalna bolest creva.^[15]^[16]^[17] Do sada su ovi lekovi prevenstveno korišteni kao antiemetici, kod ljudi i u veterinarskoj medicini.^[18]^[19]

Primeri tahikininskih antagonista su^[20]:

Tahikinin IPR008215

[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. PMID 11245256.
[2]
Carter 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. PMID 1695945.
[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 (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. PMID 7690487.
[7]
Online Mendelovsko nasleđivanje kod čoveka (OMIM) TAC1 -162320
[8]
Online Mendelovsko nasleđivanje kod čoveka (OMIM) TAC3 -162330
[9]
Alvaro G, Di Fabio R (September 2007). „Neurokinin 1 receptor antagonists--current prospects”. Curr Opin Drug Discov Devel 10 (5): 613–21. PMID 17786860.
[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. PMID 15155133.
[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. PMID 16624395.
[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. PMID 18045668.
[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. PMID 16341062.
[14]
Chahl LA (August 2006). „Tachykinins and neuropsychiatric disorders”. Curr Drug Targets 7 (8): 993–1003. DOI:10.2174/138945006778019309. PMID 16918327. Arhivirano iz originala na datum 2009-03-28. Pristupljeno 2014-04-09.
[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. PMID 16918328. Arhivirano iz originala na datum 2009-03-28. Pristupljeno 2014-04-09.
[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. PMID 16918330. Arhivirano iz originala na datum 2009-03-28. Pristupljeno 2014-04-09.
[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. PMID 17170385.
[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. PMID 18042005.
[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. PMID 18471143.
[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. PMID 16918326. Arhivirano iz originala na datum 2009-03-28. Pristupljeno 2014-04-09.

MeSH Tachykinins

[pmid11245256-1] [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. PMID 11245256.

[Carter-2] [2]
Carter 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. PMID 1695945.

[PUB00000127-3] [3]
Maggio JE (1988). „Tachykinins”. Annu. Rev. Neurosci. 11: 13–28. DOI:10.1146/annurev.ne.11.030188.000305. PMID 3284438.

[PUB00001502-4] [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.

[PUB00003623-5] [5]
Avanov AIa (1992). „Tachykinins and conformational aspects of their interactions with receptors”. Mol. Biol. (Mosk) 26 (1): 5–24. PMID 1324401.

[6] [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. PMID 7690487.

[7] [7]
Online Mendelovsko nasleđivanje kod čoveka (OMIM) TAC1 -162320

[8] [8]
Online Mendelovsko nasleđivanje kod čoveka (OMIM) TAC3 -162330

[9] [9]
Alvaro G, Di Fabio R (September 2007). „Neurokinin 1 receptor antagonists--current prospects”. Curr Opin Drug Discov Devel 10 (5): 613–21. PMID 17786860.

[10] [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. PMID 15155133.

[11] [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. PMID 16624395.

[12] [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. PMID 18045668.

[13] [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. PMID 16341062.

[14] [14]
Chahl LA (August 2006). „Tachykinins and neuropsychiatric disorders”. Curr Drug Targets 7 (8): 993–1003. DOI:10.2174/138945006778019309. PMID 16918327. Arhivirano iz originala na datum 2009-03-28. Pristupljeno 2014-04-09.

[15] [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. PMID 16918328. Arhivirano iz originala na datum 2009-03-28. Pristupljeno 2014-04-09.

[16] [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. PMID 16918330. Arhivirano iz originala na datum 2009-03-28. Pristupljeno 2014-04-09.

[17] [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. PMID 17170385.

[18] [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. PMID 18042005.

[19] [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. PMID 18471143.

[20] [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. PMID 16918326. Arhivirano iz originala na datum 2009-03-28. Pristupljeno 2014-04-09.

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Tahikinin

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