title: Activation of serotonin 5-HT₇ receptor induces coronary flow increase in isolated rat heart.
abstract: Serotonin (5-Hydroxytryptamine, 5-HT) can elicit both vasoconstrictive and relaxant responses on rat coronary artery. The constrictive response has been well discussed, but the mechanism of relaxant response is less studied. In the present study, we found serotonin (0.3 and 1 μM) increased coronary flow on isolated rat hearts, and treatment of nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) 300 μM reduced but not totally blocked this coronary flow increasing effect. In L-NAME 10 μM treated heart, treatment of selective serotonin 5-HT₇ receptor antagonist SB269970 0.1 μM blocked serotonin induced coronary flow increasing response, and in the presence of 1 μM SB269970, serotonin turned into reducing coronary flow. Treatment of TCW295 (8-(2,4-Dimethoxyphenyl)-6-methoxy-2-phenethyl-1,2,3,4-tetrahydroisoquinolin-7-ol hydrochloride), a novel serotonin 5-HT₂A/₇ receptor antagonist, inhibited both serotonin induced coronary flow increasing and decreasing effects. In conclusion, we found serotonin increases coronary flow of isolated rat heart by activating serotonin 5-HT₇ receptor activation, and this effect can be, at least partially, resistant to L-NAME.
authors.affiliation: Institute of Pharmacology, College of Medicine, National Taiwan University, 11F No.1 s.1, Ren-ai Rd., Taipei 10051 Taiwan. Electronic address: d95443008@ntu.edu.tw.
authors.forename: Ching-Chia
authors.initials: CC
authors.lastname: Chang Chien
authors.affiliation: School of Pharmacy, Molecular Probes Development Core, Molecular Imaging Center, and Center for Innovative Therapeutics Discovery, National Taiwan University, 17, Xuzhou Road, Room 936, Taipei 10055, Taiwan. Electronic address: lwhsin@ntu.edu.tw.
authors.forename: Ling-Wei
authors.initials: LW
authors.lastname: Hsin
authors.affiliation: Institute of Pharmacology, College of Medicine, National Taiwan University, 11F No.1 s.1, Ren-ai Rd., Taipei 10051 Taiwan. Electronic address: mingja@ntu.edu.tw.
authors.forename: Ming-Jai
authors.initials: MJ
authors.lastname: Su
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D007546:Isoquinolines; D010636:Phenols; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D012701:Serotonin; C039109:isoquinoline; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester
keywords: 5-HT(2A); 5-HT(7); Coronary flow; Nitric oxide; Serotonin