Abstract
The effects of 5-hydroxytriptamine (5-HT, serotonin) are mediated via five main receptor types of which the 5-HT7 receptor is the most recently characterised member. The 5-HT7 receptor has been shown to participate in mediating cranial blood vessels dilatation that may result in migraine headache. We report here the cDNA cloning, sequencing and tissue distribution of porcine 5-HT7 receptor and illustrate its comparison with corresponding receptor of known species. Employing a combination of reverse transcriptase and inverse polymerase chain reaction we amplified and sequenced a full length cDNA from the porcine cerebral cortex. The deduced amino acid sequence comparison confirmed that the cloned porcine receptor belongs to 5-HT7 receptor as described for human and other species and showing overall homology of 92–96%. The expression of 5-HT7 receptor mRNA was observed in porcine central (cerebral cortex, trigeminal ganglion and cerebellum) as well as in peripheral (pulmonary and coronary arteries, superior vena cava and saphenous vein) tissues. The established cDNA sequence and tissue distribution of porcine 5-HT7 receptor will be helpful in exploring the role of this receptor in pathophysiological processes and to predict as a potential therapeutic target for antimigraine drug development.
Similar content being viewed by others
References
Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PPA: International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 46: 157–203, 1994
Saxena P, De Vries P, Villalon C: 5-HT1-like receptors: A time to bid goodbye. Trends Pharmacol Sci 19: 311–319, 1998
Martin GR: 5-Hydroxytrptamine receptors. In: IUPHAR Committee on Receptor Nomenclature and Drug Classification (eds). IUPHAR Media, London, 1998, pp 167–185
Eglen RM, Jasper JR, Chang DJ, Martin GR: The 5-HT7 receptor: Orphan found. Trends Pharmacol Sci 18: 104–107, 1997
Vanhoenacker P, Haegeman G, Leysen JE: 5-HT7 receptors: Current knowledge and future prospects. Trends Pharmacol Sci 21: 70–77, 2000
Terrón JA, Falcón-Neri A: Pharmacological evidence for the 5-HT7 receptor mediating smooth muscle relaxation in canine cerebral arteries. Br J Pharmacol 127: 609–616, 1999
Villalón CM, Sánchez-López A, Centurión D, Saxena PR: Unravelling the pharmacological profile of the canine external carotid vasodilator ‘5-HT1-like’ receptors: Coexistence of sympatho-inhibitory 5-HT1B and postjunctional 5-HT7 receptors. Naunyn-Schmiedeberg's Arch Pharmacol 363: 73–80, 2001
Villalón CM, Centurión D, Lujan-Estrada M, Terrón JA, Sánchez-López A: Mediation of 5-HT-induced external carotid vasodilatation in GR 127935-pretreated vagosympathectomized dogs by the putative 5-HT7 receptor. Br J Pharmacol 120: 1319–1327, 1997
Tfelt-Hansen P, De Vries P, Saxena PR: Triptans in migraine: A comparative review of pharmacology, pharmacokinetics and efficacy. Drugs 60: 1259–1287, 2000
Humphrey PPA, Feniuk W: Mode of action of the anti-migraine drug sumatriptan. Trends Pharmacol Sci 12: 444–446, 1991
Saxena PR: Serotonin receptors: Subtypes, functional responses and therapeutic relevance. Pharmacol Ther 66: 339–368, 1995
May A, Goadsby PJ: Pharmacological opportunities and pitfalls in the therapy of migraine. Curr Opin Neurol 14: 341–345, 2001
Hamel E, Saxena PR: 5-Hydroxytryptamine involvement in migraine. In: J. Olesen, P. Tfelt-Hansen, K.M.A. Welch (eds). Lippincott, Williams &; Wilkins, Philadelphia, 2000, pp 319–324.
Tfelt-Hansen P, Saxena PR: Antiserotonin drugs in migraine prophylaxis. In: J. Olesen, P. Tfelt-Hansen, K.M.A. Welch (eds). Lippincott, Williams &; Wilkins, Philadelphia, 2000, pp 467–476.
Shen Y, Monsma FJ Jr, Metcalf MA, Jose PA, Hamblin MW, Sibley DR: Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype. J Biol Chem 268: 18200–18204, 1993
Terrón JA, Bouchelet I, Hamel E: 5-HT7 receptor mRNA expression in human trigeminal ganglia. Neurosci Lett 302: 9–12, 2001
Ruat M, Traiffort E, Leurs R, Tardivel-Lacombe J, Diaz J, Arrang JM, Schwartz JC: Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation. Proc Natl Acad Sci USA 90: 8547–8551, 1993
Gelernter J, Rao PA, Pauls DL, Hamblin MW, Sibley DR, Kidd KK: Assignment of the 5HT7 receptor gene (HTR7) to chromosome 10q and exclusion of genetic linkage with Tourette syndrome. Genomics 26: 207–209, 1995
Heidmann DE, Metcalf MA, Kohen R, Hamblin MW: Four 5-hydroxytryptamine7 (5-HT7) receptor isoforms in human and rat produced by alternative splicing: Species differences due to altered intron-exon organization. J Neurochem 68: 1372–1381, 1997
Krobert KA, Bach T, Syversveen T, Kvingedal AM, Levy FO: The cloned human 5-HT7 receptor splice variants: A comparative characterization of their pharmacology, function and distribution. Naunyn-Schmiedeberg's Arch Pharmacol 363: 620–632, 2001
Heidmann DE, Szot P, Kohen R, Hamblin MW: Function and distribution of three rat 5-hydroxytryptamine7 (5-HT7) receptor isoforms produced by alternative splicing. Neuropharmacology 37: 1621–1632, 1998
De Vries P, Villalón CM, Saxena PR: Pharmacological aspects of experimental headache models in relation to acute antimigraine therapy. Eur J Pharmacol 375: 61–74, 1999
Bhalla P, Sharma HS, Wurch T, Pauwels PJ, Saxena PR: Molecular cloning, sequence analysis and pharmacological properties of the porcine 5-HT1D receptor. Br J Pharmacol 131: 949–957, 2000
Bhalla P, Sharma HS, Ma X, Wurch T, Pauwels PJ, Saxena PR: Molecular cloning, pharmacological properties and tissue distribution of the porcine 5-HT1B receptor. Br J Pharmacol 133: 891–901, 2001
Ponte P, Ng SY, Engel J, Gunning P, Kedes L: Evolutionary conservation in the untranslated regions of actin mRNAs: DNA sequence of a human beta-actin cDNA. Nucleic Acids Res 12: 1687–1696, 1984
Ullmer C, Schmuck K, Kalkman HO, Lubbert H: Expression of serotonin receptor mRNAs in blood vessels. FEBS Lett 370: 215–221, 1995
Bard JA, Zgombick J, Adham N, Vaysse P, Branchek TA, Weinshank RL: Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase. J Biol Chem 268: 23422–23426, 1993
Plassat JL, Amlaiky N, Hen R: Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase. Mol Pharmacol 44: 229–236, 1993
Tsou AP, Kosaka A, Bach C, Zuppan P, Yee C, Tom L, Alvarez R, Ramsey S, Bonhaus DW, Stefanich E: Cloning and expression of a 5-hydroxytryptamine7 receptor positively coupled to adenylyl cyclase. J Neurochem 63: 456–464, 1994
Lovenberg TW, Baron BM, de Lecea L, Miller JD, Prosser RA, Rea MA, Foye PE, Racke M, Slone AL, Siegel BW et al.: A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms. Neuron 11: 449–458, 1993
To ZP, Bonhaus DW, Eglen RM, Jakeman LB: Characterization and distribution of putative 5-HT7 receptors in guinea-pig brain. Br J Pharmacol 115: 107–116, 1995
Saxena PR, Villalón CM: 5-Hydroxytryptamine: A chameleon in the heart. Trends Pharmacol Sci 12: 223–227, 1991
Villalón CM, DeVries P, Saxena PR: Serotonin receptors as cardiovascular targets. Drug Discovery Today 2: 294–300, 1997
Cushing DJ, Zgombick JM, Nelson DL, Cohen ML: LY215840, a high-affinity 5-HT7 receptor ligand, blocks serotonin-induced relaxation in canine coronary artery. J Pharmacol Exp Ther 277: 1560–1566, 1996
Roberts C, Allen L, Langmead CJ, Hagan JJ, Middlemiss DN, Price GW: The effect of SB-269970, a 5-HT7 receptor antagonist, on 5-HT release from serotonergic terminals and cell bodies. Br J Pharmacol 132: 1574–1580, 2001
Lovell PJ, Bromidge SM, Dabbs S, Duckworth DM, Forbes IT, Jennings AJ, King FD, Middlemiss DN, Rahman SK, Saunders DV, Collin LL, Hagan JJ, Riley GJ, Thomas DR: A novel, potent, and selective 5-HT7 antagonist: (R)-3-(2-(2-(4-methylpiperidin-1-yl)ethyl)pyrrolidine-1-sulfonyl) phenol (SB-269970). J Med Chem 43: 342–345, 2000
Terrón JA: 5-HT7 receptor: A target for novel therapeutic avenues? Invest Drugs 1: 302–310, 1998
Saxena PR: Cranial arteriovenous shunting, an in vivo animal model for migraine. In: J. Olesen, M.A. Moskowitz (eds). Lippincott-Raven Publishers, Philadelphia, USA, 1995, pp 189–198
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bhalla, P., Saxena, P.R. & Sharma, H.S. Molecular cloning and tissue distribution of mRNA encoding procine 5-HT7 receptor and its comparison with the structure of other species. Mol Cell Biochem 238, 81–88 (2002). https://doi.org/10.1023/A:1019959121602
Issue Date:
DOI: https://doi.org/10.1023/A:1019959121602