An analysis of the actions of prostaglandin E1 on membrane currents and contraction in uterine smooth muscle.
1. The effects of prostaglandin E(1) have been studied on the transmembrane potentials, ionic currents, and contractions in isolated myometrial strips from pregnant rats by means of a double sucrose gap apparatus.2. At low concentrations (10(-8) g/ml.), prostaglandin E(1) reduced the duration (though not the amplitude) of the action potential, but significantly increased the contraction. The inward current was unchanged, as well as the phasic component of the contraction. However, the tonic contraction, recorded when the transmembrane calcium influx was blocked selectively with D 600, was stimulated significantly, and the outward current secondarily increased.3. At maximally effective doses (10(-6) g/ml.), the electrical response to prostaglandin E(1) consisted of a slight depolarization, while a large contracture developed. The depolarization and contracture were unaffected by the removal of external calcium. The inward current was reduced by prostaglandin E(1) and the reversal potential was shifted towards less positive values of voltage, indicating a decrease in the driving force and consequently, an increase in the internal calcium concentration.4. Dibutyryl-c-AMP (5 x 10(-4)M) produced a marked relaxation of the resting tension and a slight hyperpolarization of the uterine membrane. Under these conditions, a triggered action potential was able to evoke a larger contractile response. However, prostaglandin E(1) is known to increase tissue c-AMP, so that its contractile effect cannot be mediated by c-AMP.5. It is suggested that prostaglandin E(1) acts essentially by increasing the intracellular calcium concentration. This might result from the translocation of membrane-bound calcium from surface microvesicles or sarcoplasmic reticulum. The increase in internal calcium concentration could, in turn, lead to an increase in the outward current intensity.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects*; D011247:Pregnancy; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D014599:Uterus / Q000187:drug effects*
D011458:Prostaglandins E; D005711:Gallopamil; D003994:Bucladesine; D002118:Calcium