5-HT5A receptor

5-hidroksitriptaminski (serotoninski) receptor 5A
Identifikatori
Simboli	HTR5A; 5-HT5A; MGC138226
Vanjski ID	OMIM: 601305 MGI: 96283 HomoloGene: 22461 IUPHAR: 5-ht5a GeneCards: HTR5A Gene
Ontologija gena
Molekularna funkcija	• aktivnost rodopsinu-sličnog receptora • receptorska aktivnost • aktivnost serotoninskog receptora
Celularna komponenta	• integralno sa ćelijskom membranom • membrana
Biološki proces	• prenos signala • signalni put G-protein spregnutog receptora
Pregled RNK izražavanja
	podaci
Ortolozi

edit

5-HT5A (5-hidroksitriptaminski (serotoninski) receptor 5A, HTR5A) je protein koji je kod ljudi kodiran HTR5A genom.^[1]^[2]

Funkcija

Protein kodiran 5-HT5A genom je član familije 5-hidroksitriptaminskih receptora. Njegov endogeni ligand je 5-hidroksitriptamin. On snižava cAMP nivoe putem G_i i G_o proteina.^[3] Za ovaj protein je pokazano da delom funkcioniše putem regulacije intracelularne mobilizacije Ca²⁺.^[1]

Glodari imaju dva funkcionalna tipa 5-HT₅ receptora, 5-HT_5A i 5-HT_5B,^[4] Ljudi takože imaju 5-HT_5B gen, ali njegova kodirajuća sekvenca sadrži stop kodone, tako da taj gen nije funkcionalan, i samo je 5-HT_5A izražen u ljudskom mozgu.^[5]

Klinički značaj

Neurotransmiter serotonin (5-hidroksitriptamin, 5-HT) uzima učešće u velikom broju psihijatrijskih stanja, kao i u vazokonstriktivnim i vazodilatornim efektima.^[1]

Selektivni Ligandi

Mali broj visoko selektivnih liganda je komercijalno dostupan za 5-HT_5A receptor. Selektivna aktivacija ovog receptora se može ostvariti korištenjem neselektivnog agonista serotoninskog receptor 5-karboksamidotriptamina u kombinaciji sa selektivnim antagonistima za druge ciljeve (primarno 5-HT_1A, 5-HT_1B, 5-HT_1D i 5-HT₇).^[6]^[7]

Agonisti

Valerenska kiselina, komponenta valerijana, deluje kao 5HT_5A parcijalni agonist.^[8]
DE19900637A1, selektivni ligand, K_i = 124 nM.^[9]

Antagonisti

Latrepirdin (nije selektivan)^[10]
SB-699,551

Povezano

5-HT receptor

Reference

↑ ^1,0 ^1,1 ^1,2 „Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A”.
↑ Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M (December 1994). „Cloning and characterisation of the human 5-HT5A serotonin receptor”. FEBS Lett. 355 (3): 242–6. DOI:10.1016/0014-5793(94)01209-1. PMID 7988681.
↑ Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE (November 1998). „The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells”. Eur. J. Pharmacol. 361 (2-3): 299–309. DOI:10.1016/S0014-2999(98)00744-4. PMID 9865521.
↑ Matthes H, Boschert U, Amlaiky N, Grailhe R, Plassat JL, Muscatelli F, Mattei MG, Hen R (March 1993). „Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization”. Mol. Pharmacol. 43 (3): 313–9. PMID 8450829. Arhivirano iz originala na datum 2008-12-02. Pristupljeno 2014-05-02.
↑ Nelson DL (February 2004). „5-HT5 receptors”. Curr Drug Targets CNS Neurol Disord 3 (1): 53–8. DOI:10.2174/1568007043482606. PMID 14965244.
↑ Wesołowska A (2002). „In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors”. Pol J Pharmacol 54 (4): 327–41. PMID 12523486. Arhivirano iz originala na datum 2023-09-19. Pristupljeno 2014-05-02.
↑ Peters JU, Lübbers T, Alanine A, Kolczewski S, Blasco F, Steward L (January 2008). „Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: optimising brain penetration”. Bioorg. Med. Chem. Lett. 18 (1): 262–6. DOI:10.1016/j.bmcl.2007.10.078. PMID 18023344.
↑ Dietz BM, Mahady GB, Pauli GF, Farnsworth NR (August 2005). „Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro”. Brain Res. Mol. Brain Res. 138 (2): 191–7. DOI:10.1016/j.molbrainres.2005.04.009. PMID 15921820.
↑ Garcia-Ladona Francisco Javier, Szabo Laszlo, Steiner Gerd, Hofmann Hans-Peter (2004-06-15). US patent 6750221, Use of 5-HT5-ligands in the treatment of neurodegenerative and neuropsychiatric disturbances
↑ Wu J, Li Q, Bezprozvanny I (2008). „Evaluation of Dimebon in cellular model of Huntington's disease”. Mol Neurodegener 3 (1): 15. DOI:10.1186/1750-1326-3-15. PMC 2577671. PMID 18939977.

Literatura

Raymond JR, Mukhin YV, Gelasco A, et al. (2002). „Multiplicity of mechanisms of serotonin receptor signal transduction.”. Pharmacol. Ther. 92 (2-3): 179–212. DOI:10.1016/S0163-7258(01)00169-3. PMID 11916537.
Thomas DR (2006). „5-ht5A receptors as a therapeutic target.”. Pharmacol. Ther. 111 (3): 707–14. DOI:10.1016/j.pharmthera.2005.12.006. PMID 16516972.
Rees S, den Daas I, Foord S, et al. (1995). „Cloning and characterisation of the human 5-HT5A serotonin receptor.”. FEBS Lett. 355 (3): 242–6. DOI:10.1016/0014-5793(94)01209-1. PMID 7988681.
Schanen NC, Scherer SW, Tsui LC, Francke U (1997). „Assignment of the 5-hydroxytryptamine (serotonin) receptor 5A gene (HTR5A) to human chromosome band 7q36.1.”. Cytogenet. Cell Genet. 72 (2-3): 187–8. DOI:10.1159/000134184. PMID 8978771.
„Toward a complete human genome sequence.”. Genome Res. 8 (11): 1097–108. 1999. DOI:10.1101/gr.8.11.1097. PMID 9847074.
Francken BJ, Josson K, Lijnen P, et al. (2000). „Human 5-hydroxytryptamine(5A) receptors activate coexpressed G(i) and G(o) proteins in Spodoptera frugiperda 9 cells.”. Mol. Pharmacol. 57 (5): 1034–44. PMID 10779389.
Marazziti D, Ori M, Nardini M, et al. (2001). „mRNA expression of serotonin receptors of type 2C and 5A in human resting lymphocytes.”. Neuropsychobiology 43 (3): 123–6. DOI:10.1159/000054878. PMID 11287788.
Iwata N, Ozaki N, Inada T, Goldman D (2001). „Association of a 5-HT(5A) receptor polymorphism, Pro15Ser, to schizophrenia.”. Mol. Psychiatry 6 (2): 217–9. DOI:10.1038/sj.mp.4000829. PMID 11317225.
Grailhe R, Grabtree GW, Hen R (2001). „Human 5-HT(5) receptors: the 5-HT(5A) receptor is functional but the 5-HT(5B) receptor was lost during mammalian evolution.”. Eur. J. Pharmacol. 418 (3): 157–67. DOI:10.1016/S0014-2999(01)00933-5. PMID 11343685.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). „Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.”. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. DOI:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Noda M, Yasuda S, Okada M, et al. (2003). „Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways.”. J. Neurochem. 84 (2): 222–32. DOI:10.1046/j.1471-4159.2003.01518.x. PMID 12558985.
Scherer SW, Cheung J, MacDonald JR, et al. (2003). „Human chromosome 7: DNA sequence and biology.”. Science 300 (5620): 767–72. DOI:10.1126/science.1083423. PMC 2882961. PMID 12690205.
Hillier LW, Fulton RS, Fulton LA, et al. (2003). „The DNA sequence of human chromosome 7.”. Nature 424 (6945): 157–64. DOI:10.1038/nature01782. PMID 12853948.
Khorana N, Smith C, Herrick-Davis K, et al. (2003). „Binding of tetrahydrocarboline derivatives at human 5-HT5A receptors.”. J. Med. Chem. 46 (18): 3930–7. DOI:10.1021/jm030080s. PMID 12930153.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). „Complete sequencing and characterization of 21,243 full-length human cDNAs.”. Nat. Genet. 36 (1): 40–5. DOI:10.1038/ng1285. PMID 14702039.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). „The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”. Genome Res. 14 (10B): 2121–7. DOI:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Dietz BM, Mahady GB, Pauli GF, Farnsworth NR (2005). „Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro.”. Brain Res. Mol. Brain Res. 138 (2): 191–7. DOI:10.1016/j.molbrainres.2005.04.009. PMID 15921820.

Vanjske veze

„5-ht_5a”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2014-02-26.

[entrez-1] 1,0 ^1,1 ^1,2 „Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A”.

[pmid7988681-2] Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M (December 1994). „Cloning and characterisation of the human 5-HT5A serotonin receptor”. FEBS Lett. 355 (3): 242–6. DOI:10.1016/0014-5793(94)01209-1. PMID 7988681.

[pmid9865521-3] Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE (November 1998). „The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells”. Eur. J. Pharmacol. 361 (2-3): 299–309. DOI:10.1016/S0014-2999(98)00744-4. PMID 9865521.

[pmid8450829-4] Matthes H, Boschert U, Amlaiky N, Grailhe R, Plassat JL, Muscatelli F, Mattei MG, Hen R (March 1993). „Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization”. Mol. Pharmacol. 43 (3): 313–9. PMID 8450829. Arhivirano iz originala na datum 2008-12-02. Pristupljeno 2014-05-02.

[pmid14965244-5] Nelson DL (February 2004). „5-HT5 receptors”. Curr Drug Targets CNS Neurol Disord 3 (1): 53–8. DOI:10.2174/1568007043482606. PMID 14965244.

[pmid12523486-6] Wesołowska A (2002). „In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors”. Pol J Pharmacol 54 (4): 327–41. PMID 12523486. Arhivirano iz originala na datum 2023-09-19. Pristupljeno 2014-05-02.

[pmid18023344-7] Peters JU, Lübbers T, Alanine A, Kolczewski S, Blasco F, Steward L (January 2008). „Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: optimising brain penetration”. Bioorg. Med. Chem. Lett. 18 (1): 262–6. DOI:10.1016/j.bmcl.2007.10.078. PMID 18023344.

[pmid15921820-8] Dietz BM, Mahady GB, Pauli GF, Farnsworth NR (August 2005). „Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro”. Brain Res. Mol. Brain Res. 138 (2): 191–7. DOI:10.1016/j.molbrainres.2005.04.009. PMID 15921820.

[US6750221-9] Garcia-Ladona Francisco Javier, Szabo Laszlo, Steiner Gerd, Hofmann Hans-Peter (2004-06-15). US patent 6750221, Use of 5-HT5-ligands in the treatment of neurodegenerative and neuropsychiatric disturbances

[pmid18939977-10] Wu J, Li Q, Bezprozvanny I (2008). „Evaluation of Dimebon in cellular model of Huntington's disease”. Mol Neurodegener 3 (1): 15. DOI:10.1186/1750-1326-3-15. PMC 2577671. PMID 18939977.

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