Regional differences in the prostanoid receptors mediating prostaglandin F2 alpha-induced contractions of cat isolated arteries.
U46619, a stable thromboxane A2 (TXA2) mimetic, and prostaglandin F2 alpha (PGF2 alpha) contracted helical strips of cat coronary, renal and mesenteric arteries in a concentration-dependent manner. The EC50 values for U46619 did not differ significantly in these arteries, but those for PGF2 alpha were in the order of coronary less than renal less than mesenteric arteries. Contractions induced by U46619 were antagonized by S-145, a selective TXA2 receptor antagonist, with similar activity in these arteries. On the other hand, contractions induced by low concentrations of PGF2 alpha (10(-9) to 10(-7) M) were not influenced by treatment with S-145 in coronary arteries, although those induced by high concentrations (5 x 10(-7) to 10(-5) M) were partially attenuated. These contractions resistant to the TXA2 antagonist were antagonized by diphloretin phosphate (DPP), a non-selective PG antagonist. Contractions induced by PGF2 alpha (5 x 10(-7) to 5 x 10(-5) M) in mesenteric arteries were inhibited by S-145 in a concentration-dependent manner. Contractions induced by PGF2 alpha in renal arteries were partially inhibited by S-145. The inhibitory activity of S-145 to PGF2 alpha-induced contractions at EC50 was in the order of coronary less than renal less than mesenteric arteries. Treatment with indomethacin slightly potentiated the contractions induced by PGF2 alpha in mesenteric arteries. Removal of the endothelium did not affect the contractile responses induced by PGF2 alpha and the inhibitory activity of S-145 in the arteries. These results suggest that the contractile responses induced by low concentrations of PGF2 alpha (up to 10(-7) M) are associated with their action via PG receptor(s), which is different from TXA2 receptor, and those induced by high concentrations of PGF2 alpha (5 x 10(-7) M or higher) interact with TXA2 receptors in cat vascular smooth muscles. It appears that the functional expression of this PG receptor(s) is greater in coronary arteries than in renal arteries, and that it is not found in mesenteric arteries.
Nakajima
M
M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Ueda
M
M
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002415:Cats; D003326:Coronary Circulation / Q000187:drug effects; D015237:Dinoprost / Q000502:physiology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011121:Polyphloretin Phosphate / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects
D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D011448:Prostaglandin Antagonists; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; C056566:S 145; C013509:diphloretin phosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011121:Polyphloretin Phosphate; D015237:Dinoprost; D007213:Indomethacin