Antagonism of prostanoid-induced vascular contraction by 13-azaprostanoic acid (13-APA).
Isometric contractions in vitro of helically cut strips of canine mesenteric arteries (O.D. = 0.6-1 mm) were recorded in the presence of 10 microM indomethacin. PGF2 alpha PGE2, U-46619 (TXA2 mimetic), norepinephrine, 5-hydroxytryptamine, and KCl produced dose-related contractions. The EC50 values of the prostanoids in the control period were: PGF2 alpha, 7.3 +/- 0.7 X 10(-7) M; PGE2, 2.1 +/- 0.2 X 10(-6) M; and U-46619, 4.1 +/- 1.0 X 10(-10) M. Exposure to 13-azaprostanoic acid (13-APA), 5 X 10(-5) M and 2 X 10(-4) M, for 20 min caused parallel and dose-related shifts to the right of the dose-response curves generated by all three prostanoids without affecting the contractile responses to KCl, norepinephrine, or 5-hydroxytryptamine or relaxation induced by PGI2. 13-APA, at the concentrations used, had no agonist activity. Small contractions (10-15%) seen on the addition of 13-APA to the baths were found to be related to the alcohol content of the solvent. Dose ratios (with/without antagonist) at the EC50 level were found to be: in the presence of 5 X 10(-5) M 13-APA PGF2 alpha, 2.7 +/- 0.3; PGE2, 3.5 +/- 0.9; U-46619, 5.2 +/- 0.9; in the presence of 2 X 10(-4) M 13-APA PGF2 alpha, 17.1 +/- 3; PGE2, greater than 50; and U-46619, 23.3 +/- 5.7. Thus, 13-APA is a specific antagonist of these prostanoids with no agonist activity of its own.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D015237:Dinoprost; D015232:Dinoprostone; D004285:Dogs; D000431:Ethanol / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011448:Prostaglandin Antagonists; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D011466:Prostanoic Acids / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors*
D005227:Fatty Acids; D011448:Prostaglandin Antagonists; D011450:Prostaglandin Endoperoxides, Synthetic; D011458:Prostaglandins E; D011460:Prostaglandins F; D011466:Prostanoic Acids; D014662:Vasoconstrictor Agents; D012701:Serotonin; D000431:Ethanol; D011189:Potassium Chloride; C022574:13-azaprostanoic acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; D015232:Dinoprostone; D009638:Norepinephrine