title: GR-127935-sensitive mechanism mediating hypotension in anesthetized rats: are 5-HT5B receptors involved?
abstract: The 5-HT1B/1D receptor antagonist, GR-127935, inhibits hypotensive responses produced by the 5-HT1A, 5-HT1B/1D and 5-HT7 receptor agonist, and 5-HT5A/5B receptor ligand, 5-carboxamidotryptamine (5-CT), in rats. This work further characterized the above mechanism using more selective 5-HT1B and 5-HT1D receptor antagonists. Also, expression of 5-HT5A and 5-HT5B receptor mRNAs in blood vessels was searched by reverse transcription polymerase chain reaction. Decreases in diastolic blood pressure induced by 5-CT (0.001-10 μg/kg, intravenously) were analyzed in anesthetized rats that had received intravenous vehicle (1 mL/kg), SB-224289 (5-HT1B antagonist; 0.3 and 1.0 mg/kg), BRL15572 (5-HT1D antagonist; 0.3 and 1.0 mg/kg), SB-224289 + BRL15572 (0.3 mg/kg, each), or SB-224289 + BRL15572 (0.3 mg/kg, each) + GR-127935 (1 mg/kg). Because only the latter treatment inhibited 5-CT-induced hypotension, suggestive of a mechanism unrelated to 5-HT1B/1D receptors, the effects of antagonists/ligands at 5-HT5A (SB-699551, 1 mg/kg), 5-HT6 (SB-399885, 1 mg/kg), and 5-HT1B/1D/5A/5B/7 receptors (ergotamine, 0.1 mg/kg) on 5-CT-induced hypotension were tested. Interestingly, only ergotamine blocked 5-CT-induced responses; this effect closely paralleled that of SB-224289 + BRL-15572 + GR-127935. Neither did ergotamine nor GR-127935 inhibit hypotensive responses induced by the 5-HT7 receptor agonist, LP-44. Faint but clear bands corresponding to 5-HT5A and 5-HT5B receptor mRNAs in aorta and mesenteric arteries were detected. Results suggest that the GR-127935-sensitive mechanism mediating hypotension in rats is unrelated to 5-HT1B, 5-HT1D, 5-HT5A, 5-HT6, and 5-HT7 receptors. This mechanism, however, resembles putative 5-HT5B receptors.
authors.affiliation: *Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Apartado Postal 14-740, Zacatenco 07000, México DF, México; †Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina-IPN, Plan de San Luis y Díaz Mirón s/n, Casco de Sto Tomás, México DF, México; and ‡Dipartimento Farmaco-Chimico, Universitá degli Studi di Bari, Bari, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Sánchez-Maldonado
authors.forename: Pedro
authors.initials: P
authors.lastname: López-Sánchez
authors.forename: Liliana
authors.initials: L
authors.lastname: Anguiano-Robledo
authors.forename: Marcello
authors.initials: M
authors.lastname: Leopoldo
authors.forename: Enza
authors.initials: E
authors.lastname: Lacivita
authors.forename: José A
authors.initials: JA
authors.lastname: Terrón
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004878:Ergotamine / Q000494:pharmacology; D007022:Hypotension / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D010881:Piperidones / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology
chemical_list: D001713:Biphenyl Compounds; D010069:Oxadiazoles; D010879:Piperazines; D010881:Piperidones; D011985:Receptors, Serotonin; C108518:SB 22489G; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; C104425:serotonin 7 receptor; C090701:GR 127935; D012701:Serotonin; C047087:5-carboxamidotryptamine; C108532:BRL 15572; D004878:Ergotamine