Mesenteric vasoconstrictor response to 5-hydroxytryptamine in the in situ blood autoperfused rat mesentery: involvement of 5-HT(2B) and/or 5-HT(2C) receptor activation.
Using a number of agonist and antagonist compounds, we attempted to characterize the responses and receptors involved in the effects of 5-hydroxytryptamine (5-HT) in the in situ blood perfused rat mesentery. An intra-arterial (i.a.) bolus injection of 5-HT increased mesenteric perfusion pressure in a dose-dependent way but did not change the systemic blood pressure. The selective 5-HT(2) receptor agonists alpha-methyl-5-HT, 1-(3-chlorophenyl)piperazine dihydrochloride (m-CPP) and (+/-)-1-(4-iodo-2, 5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI), caused a local vasoconstrictor effect in the autoperfused vascular mesenteric bed. Intra-arterial injection of 5-carboxamidotryptamine (5-CT) and 1-(m-chlorophenyl)-biguanide (m-CPBG) did not modify the mesenteric perfusion pressure. The vasoconstrictor effect elicited by 5-HT and alpha-methyl-5-HT was significantly decreased by ritanserin and by a selective 5-HT(2B/2C) receptor antagonist, N-3-pyridinyl-3, 5-dihydro-5-methyl-benzo[1,2-b:4,5-b']dipyrrole-1(2H)-carboxamide hydrochloride (SB 206553), but was not modified by prazosin, propranolol, indomethacin or enalapril pretreatment. Our data suggest that the vasoconstrictor serotonergic response induced in the in situ autoperfused rat mesenteric vascular bed is mainly mediated by activation of 5-HT(2B) and/or 5-HT(2C) receptors.
Fernández
M M
MM
Laboratorio de Farmacognosia y Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, 37007, Salamanca, Spain.
Morán
A
A
Martín
M L
ML
San Román
L
L
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D008643:Mesentery / Q000098:blood supply / Q000187:drug effects*; D010477:Perfusion; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D000662:Amphetamines; D001645:Biguanides; D007211:Indoles; D010879:Piperazines; D011725:Pyridines; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D016713:Ritanserin; C042390:alpha-methylserotonin; D012701:Serotonin; D004656:Enalapril; C065734:1-(3-chlorophenyl)biguanide; C047087:5-carboxamidotryptamine; D011433:Propranolol; C094868:SB 206553; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C015068:1-(3-chlorophenyl)piperazine; D011224:Prazosin; D007213:Indomethacin