Pharmacological evidence that 5-HT(1B/1D) receptors mediate hypotension in anesthetized rats.
5-Carboxamidotryptamine (5-CT; 0.003-310 microg/kg, i.v.) produced dose-dependent hypotensive responses which were blocked in a complex manner by the 5-HT(7) receptor antagonist, (R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl) ethyl] pyrrolidine (SB-269970; 1 mg/kg, i.v.), in anesthetized vagosympathectomized rats. Interestingly, the 5-HT(1B/1D) receptor antagonist, N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl) [1,1-biphenyl]-4-carboxamide hydrochloride monohydrate GR-127935 (1 mg/kg, i.v.), also inhibited 5-CT-induced hypotension but the effect was clearly noncompetitive. Finally, the combination of GR-127935+SB-269970 (1 mg/kg, i.v., each) produced a further decreased of 5-CT-induced responses as compared to the effect of individual treatments. These data suggest that, in addition to 5-HT(7) receptors, 5-HT(1B/1D) receptors may also mediate hypotension in rats.
Terrón
José A
JA
Sección Externa de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apdo. Postal 14-740, Zacatenco 07000, México D.F., Mexico. jterron@cinvestav.mx
Sánchez-Maldonado
Carolina
C
Martínez-García
Esther
E
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D007022:Hypotension / Q000503:physiopathology*; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D044346:Receptor, Serotonin, 5-HT1D / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
C522380:5-HT(7) receptor, rat; D010069:Oxadiazoles; D010636:Phenols; D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; C404922:SB 269970; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; C090701:GR 127935; D012701:Serotonin; C047087:5-carboxamidotryptamine