Characterization of an endothelial 5-hydroxytryptamine (5-HT) receptor mediating relaxation of the porcine coronary artery.
The pharmacological properties of the endothelial 5-hydroxytryptamine (5-HT) receptors involved in relaxation of vascular smooth muscle were determined in rings of pig coronary artery contracted with 10 nmol/l of the thromboxane A2 receptor agonist 9,11-dideoxy-11 alpha,9 alpha-epoxy-methano-prostaglandin F2 alpha (U 46619). (1) In the presence of 10 mumol/l ketanserin, relaxation was obtained with: 5-HT (apparent pD2 value 7.00), 5-carboxamidotryptamine (5-CONH2-T; 6.42), 5-aminotryptamine (5-NH2-T; 5.96), 5-methoxytryptamine (5-OCH3-T; 5.92), tryptamine, 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo(1,2-a)quinoxaline maleate (CGS 12066 A) and 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole succinate (RU 24969). The maximum relaxation obtainable with the agonists was about 40-60% of the U 46619-induced contraction and the concentration-response curves for 5-HT, 5-NH2-T and 5-OCH3-T were bell-shaped. The endothelium-dependence of this effect (i.e. the failure to relax the artery in endothelium-denuded preparations) was demonstrated for 5-HT, 5-CONH2-T, RU 24969, CGS 12066A and tryptamine. (2) 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 4-hydroxytryptamine, quipazine and yohimbine were ineffective in decreasing the tension of arteries with or without endothelium. Ipsapirone elicited full relaxation of U 46619-induced contraction, but this effect was not endothelium-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
Molderings
G J
GJ
Institut für Pharmakologie und Toxikologie der Rheinischen Friedrich-Wilhelms-Universität Bonn, Federal Republic of Germany.
Engel
G
G
Roth
E
E
Göthert
M
M
D000818:Animals; D015283:Citalopram / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects; D003345:Corticosterone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006072:Gossypol / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013552:Swine
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D015283:Citalopram; D010293:Pargyline; D006072:Gossypol; D003345:Corticosterone; D007213:Indomethacin; D010646:Phentolamine