Benextramine acts as an irreversible noncompetitive antagonist of U46619-mediated contraction of the rat small mesenteric artery.
We have studied the effects of benextramine on the U46619 (11 alpha,9 alpha-epoxymethano-15S-hydroxy-prosta-5Z,13E-dienoic acid)-mediated contraction of the rat isolated small mesenteric artery. U46619 (10 nM-10 microM) produced a concentration-dependent contraction of the small mesenteric artery. The selective prostanoid TP receptor antagonist, SQ 30,741 ([1S-[1 alpha,2 alpha(5Z),3 alpha,4 alpha]]-7- [[[[[(oxaheptyl)amino]acetyl]amino]-methyl]-7-oxabicyclo[2.2.1]hep t-2-yl]-5- heptenoic acid; 1 microM), produced a parallel, rightward shift of the U46619 curve with an associated pA2 value of 7.43 +/- 0.09. Treatment of tissues with 100 microM benextramine depressed the maximum response to U46619 in a time-dependent manner. However, neither SQ 30,741 (10 microM) nor U46619 (10 microM) incubation significantly protected against this effect. Thus, benextramine acts as an irreversible noncompetitive antagonist of U46619. The mechanism of this action is not yet clear.
Van der Graaf
P H
PH
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Netherlands.
Stam
W B
WB
Saxena
P R
PR
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003538:Cystamine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; C029998:benextramine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003538:Cystamine