Mediation by 5-hydroxytryptamine2B receptors of endothelium-dependent relaxation in rat jugular vein.
1. An 'atypical' 5-HT2 receptor which is located on the endothelium of rat jugular vein has been described. In the present study we have further defined the nature of the 5-HT2 receptor subtype present in this preparation. 2. In experiments conducted in the presence of ketanserin to preclude involvement of 5-HT2 receptors, the mixed 5-HT2B/2C antagonist, SB 200646, acted as an antagonist of 5-HT at the endothelial 5-HT receptor (pA2 = 7.2). Yohimbine, which exhibits negligible affinity for rat 5-HT2C receptors but has high 5-HT2B receptor affinity, acted as a potent but non-surmountable antagonist (pA2 > or = 7.3) in rat jugular vein. Neither yohimbine nor SB 200646 affected endothelium-dependent relaxations induced by carbachol. 3. Mianserin also acted as a surmountable antagonist (pA2 = 7.3) and the 5-HT2B agonist, BW 723C86, acted as a potent partial agonist (pEC50 [95% C L], intrinsic activity +/- s.e. mean = 7.9 [7.6-8.3], 0.84 +/- 0.04). Responses to BW 723C86 were antagonized by SB 200646 (0.3 microM) yielding an 'apparent' pA2 [95% CL] of 7.03 [6.76-7.32]. 4. These data are consistent with the presence of 5-HT2B receptors mediating endothelium-dependent relaxation of rat jugular vein.
Ellis
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SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex.
Byrne
C
C
Murphy
O E
OE
Tilford
N S
NS
Baxter
G S
GS
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007601:Jugular Veins / Q000187:drug effects; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
C092430:1-(5-(2-thenyloxy)-1H-indol-3-yl)propan-2-amine; D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013876:Thiophenes; C080864:N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea; D008803:Mianserin; D015016:Yohimbine; D012701:Serotonin; D014508:Urea; D002217:Carbachol