Prompt effect of progesterone on the adrenergic response of smooth muscles

The contractile effects of epinephrine on the uterus and ductus deferens of the rabbit and the ductus deferens of the monkey were inhibited by the preincubation with progesterone (6.4 X 10(-5) M) for 1 or 3 min in Locke-Ringer solution. Epinephrine relaxed the guinea pig uterus and taenia caecum. The relaxant effects were enhanced by preincubation with progesterone. Their effects were in a dose-dependent manner. There was no apparent change in the number and affinity of alpha-adrenergic receptors in the uterus of rabbits and the ductus deferens of guinea pigs during the incubation with progesterone. Progesterone has no direct effect on alpha-adrenergic receptors. All smooth muscles yielded reproducible contractile reactions to Ca2+ when maintained in depolarizing Tyrode's solution containing K+ (40 mmol/l). Their concentration-response curves were inhibited by preincubation with progesterone (6.4 X 10(-5) M), and they were shifted to the right in a concentration-dependent manner. Established Ca2+-induced contractions were rapidly relaxed by the addition of progesterone (6.4 X 10(-5) M). It suggests that progesterone directly affects the plasma membrane and inhibits the voltage-dependent Ca2+ channel and then inhibits smooth muscle contraction.