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

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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 β-escin - treated skinned strips (membrane-permeable conditions and chemical clamping of intracellular Ca ++ concentrations). The effects of guanosine 5'-0-( γ-thiotriphosphate) (a nonhydrolyzable analog of guanosine 5'-triphosphate), prostaglandin F 2α 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 β-escin - treated skinned myometrial strips from late gestation, 0.3 μmol/L Ca ++ evoked contractions. Carbachol (10 μmol/L) plus guanosine 5'-triphosphate (10 μmol/L) enhanced the 0.3 μmol/L Ca ++-induced contractions of skinned strips; the increase was antagonized by 1 mmol/L guanosine 5'-0-( β-thiodiphosphate). Guanosine 5'-0-( γ-thiotriphospate) (0.1 to 100 μmol/L), prostaglandin F 2α (10 μmol/L) plus guanosine 5'-triphosphate (10 μmol/L), prostaglandin E 2 (10 μmol/L) plus guanosine 5'-triphosphate (10 μmol/L), and okadaic acid (1 nmol/L) also augmented 0.3 μmol/L Ca ++ contractions in skinned strips. The increases of 0.3 μmol/L Ca ++-induced contractility by the agonists with guanosine 5'-triphosphate or guanosine 5'-0-( γ-thiotriphosphate) were similar between late gestation and delivery. CONCLUSION: These results suggest that agonists such as carbachol, prostaglandin F 2α , 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. (Am J Obstet Gynecol 1996;175:199-206.)