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

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.

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'-0-(gamma-thiotriphosphate) (a nonhydrolyzable analog of guanosine 5'-triphosphate), prostaglandin F2 alpha with guanosine 5'-triphosphate, prostaglandin E2 with guanosine 5'-triphosphate, and okadaic acid (a phosphatase inhibitor) were also examined in skinned strips.

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 mumol/L Ca++ evoked contractions. Carbachol (10 mumol/L) plus guanosine 5'-triphosphate (10 mumol/L) enhanced the 0.3 mumol/L Ca(++)-induced contractions of skinned strips; the increase was antagonized by 1 mmol/L guanosine 5'-0-(beta-thiodiphosphate). Guanosine 5'-0-(gamma-thiotriphosphate) (0.1 to 100 mumol/L), prostaglandin F2 alpha (10 mumol/L) plus guanosine 5'-triphosphate (10 mumol/L), prostaglandin E2 (10 mumol/L) plus guanosine 5'-triphosphate (10 mumol/L), and okadaic acid (1 nmol/L) also augmented 0.3 mumol/L Ca++ contractions in skinned strips. The increases of 0.3 mumol/L Ca(++)-induced contractility by the agonists with guanosine 5'-triphosphate or guanosine 5'-0-(gamma-thiotriphosphate) were similar between late gestation and delivery.

These results suggest that agonists such as carbachol, prostaglandin F2 alpha, and prostaglandin E2 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.