American journal of obstetrics and gynecology · 1996
Agonists increase the sensitivity of contractile elements for Ca++ in pregnant rat myometrium.
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Izumi H, Bian K, Bukoski R D, Garfield R E
Аннотация
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'-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.
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 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.
CONCLUSION: 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.
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'-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.
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 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.
CONCLUSION: 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.