Agonists increase the sensitivity of contractile elements for Ca++ in pregnant rat myometrium

OBJECTIVE: The effects of agonists and guanosine 5'-triphosphate binding proteins (G proteins) on contractile properties were investigated in rat longitudinal myometrial tissues in late gestation and during delivery. STUDY DESIGN: The effect of carbachol was examined on the intracellular Ca++ concentration in intact thin muscle strips from pregnant rat myometrium. In addition, the action of carbachol with guanosine 5'-triphosphate was examined on the Ca++-induced contractions in beta-escin-treated skinned strips (membrane-permeable conditions and chemical clamping of intracellular Ca++ concentrations). The effects of guanosine 5'-O-(gamma-thiotriphosphate) (a nonhydrolyzable analog of guanosine 5'-triphosphate), prostaglandin F-2 alpha with guanosine 5'-triphosphate, prostaglandin E(2) with guanosine 5'-triphosphate, and okadaic acid (a phosphatase inhibitor) were also examined in skinned strips. RESULTS: In intact longitudinal rat myometrium at late gestation the maximum contractions induced by carbachol were larger than the maximum contractions induced by high K+ (118 mmol/L), whereas increases in intracellular Ca++ concentration produced by both agents were similar. In beta-escin-treated skinned myometrial strips from late gestation, 0.3 mu mol/L Ca++ evoked contractions. Carbachol (10 mu mol/L) plus guanosine 5'-triphosphate (10 mu mol/L) enhanced the 0.3 mu mol/L Ca++-induced contractions of skinned strips; the increase was antagonized by 1 mmol/L guanosine 5'-O-(beta-thiodiphosphate). Guanosine 5'-O-(gamma-thiotriphospate) (0.1 to 100 mu mol/L), prostaglandin F-2 alpha (10 mu mol/L) plus guanosine 5'-triphosphate (10 mu mol/L), prostaglandin E(2) (10 mu mol/L) plus guanosine 5'-triphosphate (10 mu mol/L), and okadaic acid (1 nmol/L) also augmented 0.3 mu mol/L Ca++ contractions in skinned strips. The increases of 0.3 mu mol/L Ca++-induced contractility by the agonists with guanosine 5'-triphosphate or guanosine 5'-O-(gamma-thiotriphosphate) were similar between late gestation and delivery. CONCLUSION: These results suggest that agonists such as carbachol, prostaglandin F,,, and prostaglandin E(2) enhance the Ca++-induced contraction of myometrium at late gestation through G protein-mediated mechanisms. The agonist/G protein-mediated Ca++-sensitizing effects on contractile elements produce additional contractile force with the same amount of intracellular calcium, thus providing expelling forces for delivery of the fetuses.