Synthetic FP-prostaglandin-induced contraction of rat uterus smooth muscle in vitro

Abstract

Numerous synthetic FP-class prostaglandin (PG) analogs stimulated the contraction of isolated non-pregnant female rat uterus in a concentration-dependent manner with the following agonist potencies: bimatoprost acid (17-phenyl-trinor PGF 2 α ; EC 50=0.68±0.06 nM)=cloprostenol (EC 50=0.73±0.01 nM)>travoprost acid (EC 50=1.3±0.07 nM)>latanoprost acid (EC 50=2.7±0.08 nM)>PGF 2 α (EC 50=52±11 nM)>unoprostone (UF-021; EC 50=310±101 nM)>S-1033 (EC 50=610±4 nM)>bimatoprost (EC 50=1130±173 nM). The FP-receptor antagonist, AL-8810, antagonized the contractile effects of PGF 2 α ( K i=2.9±0.2 μM), travoprost acid ( K i=0.6±0.1 μM) and bimatoprost ( K i=0.2±0.02 μM). Agonist and antagonist potencies for rat uterus contraction by these PGs compared well with their potencies for inducing/blocking functional responses in other systems ( r=0.83–0.94) except with bovine iris sphincter ( r=0.2; p<0.7). In conclusion, the rat uterus contains functionally active FP-receptors whose activation by a variety of free acid and an amide forms of synthetic PGs leads to the contraction of this tissue and which can be pharmacologically blocked by an FP-receptor antagonist, AL-8810.