Regional differences in the prostanoid receptors mediating prostaglandin F 2α-induced contractions of cat isolated arteries

Abstract

U46619, a stable thromboxane A 2 (TXA 2) mimetic, and prostaglandin F 2α (PGF 2a) contracted helical strips of cat coronary, renal and mesenteric arteries in a concentration-dependent manner. The EC 50 values for U46619 did not differ significantly in these arteries, but those for PGF 2α were in the order of coronary < renal < mesenteric arteries. Contractions induced by U46619 were antagonized by S-145, a selective TXA; receptor antagonist, with similar activity in these arteries. On the other hand, contractions induced by low concentrations of PGF 2α(10 −9 to 10 −7 M) were not influenced by treatment with S-145 in coronary arteries, although those induced by high concentrations (5 × 10 −7 to 10 −5 M) were partially attenuated. These contractions resistant to the TXA 2 antagonist were antagonized by diphloretin phosphate (DPP), a non-selective PG antagonist. Contractions induced by PGF 2α(5 × 10 −7 to 5 × 10 −5 M) in mesenteric arteries were inhibited by S-145 in a concentration-dependent manner. Contractions induced by PGF 2α in renal arteries were partially inhibited by S-145. The inhibitory activity of S-145 to PGF 2α-induced contractions at EC 50 was in the order of coronary < renal < mesenteric arteries. Treatment with indomethacin slightly potentiated the contractions induced by PGF 2α in mesenteric arteries. Removal of the endothelium did not affect the contractile responses induced by PGF 2α and the inhibitory activity of S-145 in the arteries. These results suggest that the contractile responses induced by low concentrations of PGF 2α (up to 10 −7 M) are associated with their action via PG receptor(s), which is different from TXA 2 receptor, and those induced by high concentrations of PGF 2α(5 × 10 −7 M or higher) interact with TXA; 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.