5-HT7 receptor-mediated dilatation in the middle meningeal artery of anesthetized rats.
Topical administration of 5-carboxamidotryptamine (5-CT; 0.01-1000 microM) to the exposed dura mater encephali of anesthetized rats produced decreases in blood pressure and dilatation in the middle meningeal artery. Pretreatment with 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.), unmasked meningeal dilator responses to lower concentrations of 5-CT, and attenuated those to higher concentrations; GR-127935 also inhibited 5-CT-induced hypotension. The 5-HT7 receptor antagonist, (R)-1-{(3-hydroxyphenyl)sulfonyl}-2-{2-(2-(4-methyl-1-piperidinyl) ethyl} pyrrolidine (SB-269970; 1 mg/kg, i.v.), strongly inhibited dilator and hypotensive responses to 5-CT; the combination of GR-127935+SB-269970 (1 mg/kg, i.v., each) further inhibited meningeal and hypotensive responses. Thus, 5-CT may produce dilatation in the middle meningeal artery via 5-HT7 receptors; complex effects appear to involve 5-HT(1B/1D) receptors.
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
Martínez-García
Esther
E
D000287:Administration, Topical; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004106:Dilatation; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008576:Meningeal Arteries / Q000187:drug effects / Q000502:physiology; D008578:Meninges / Q000098:blood supply / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage* / Q000494:pharmacology*
D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; D012701:Serotonin; C047087:5-carboxamidotryptamine