Characterization of prostanoid receptors mediating actions of the isoprostanes, 8‐iso‐PGE2 and 8‐iso‐PGF2α, in some isolated smooth muscle preparations

Abstract

We investigated the contracting actions of the isoprostanes (isoPs), 8‐iso‐prostaglandin (PG) F_2α and 8‐iso‐PGE₂, in comparison to the effects of the thromboxane (TX) A₂‐mimetic U 46619 and the traditional prostaglandin PGE₂ in the isolated rat aorta, isolated rat gastric fundus and the isolated guinea‐pig ileum. U 46619 and 8‐iso‐PGF_2α caused contractions in the rat aorta and rat gastric fundus in a concentration‐dependent manner, whereas these agonists showed no effects in the guinea‐pig ileum. However, 8‐iso‐PGE₂ and PGE₂ caused contractions in all isolated organs used. The prostanoid TP‐receptor antagonist SQ 29,548 (10 nM) significantly antagonized vasoconstrictions induced by the agonists used in the rat aorta. SQ 29,548 at a final concentration of 3 μM, but not at lower concentrations, significantly inhibited contractions induced by U 46619, 8‐iso‐PGF_2α and 8‐iso‐PGE₂ in the rat fundus. Responses to PGE₂ were unchanged. The prostanoid EP₁‐receptor antagonist SC 51089 (3 μM) significantly inhibited contractions induced by 8‐iso‐PGE₂ and PGE₂ in the rat fundus and in the guinea‐pig ileum. SC 51089 had no effect on responses to any of the agonists tested. Our results show that 8‐iso‐PGE₂, in contrast to 8‐iso‐PGF_2α, can also cause contractions by activation of the EP₁‐receptors in the rat gastric fundus and the guinea‐pig ileum. The findings of the present study do not support the existence of a unique isoP‐receptor in the tissues used. British Journal of Pharmacology (2000) 130, 1903–1910; doi:10.1038/sj.bjp.0703522