Characterization of the spontaneous motor activity of the isolated human pregnant myometrium

The motor activity of myometrial strips from pregnant human uterus was characterized in vitro by the use of inhibitory compounds acting on the smooth muscle contractility at different levels. Spontaneous contractions were not inhibited by tetrodotoxin or a series of membrane receptor antagonists, like anticholinergics, antihistaminics, alpha-adrenergic blocking agents, antiserotoninergics and opioid receptor antagonists, thus excluding neuronal involvements or a local release of endogenous mediators active on the respective membrane receptors. The ineffectiveness of indomethacin (10(-5) M) minimizes a role for excitatory prostaglandins. Isoprenaline and selective beta 2-adrenergic stimulants, like salbutamol and hexoprenaline (up to 10(-5) M), failed to affect the amplitude of spontaneous contractions. Conversely the adenylate cyclase activator, forskolin, had a concentration-dependent inhibitory effect. Ca2(+)-free medium, trifluoperazine and all the calcium channel blockers examined produced a concentration-dependent inhibition of the spontaneous contractions in the following order of sensitivity: nifedipine much greater than verapamil much greater than diltiazem greater than trifluoperazine. The inhibitory effect of nifedipine was not overcome by excess calcium concentration in the bathing medium, but was completely restored by addition of the calcium agonist Bay K 8644 10(-7) M. From these data it can be concluded that the spontaneous activity of pregnant human myometrium in vitro is independent of neural or humoral mechanisms. The inhibitory effect of Ca(+)-free medium and the efficacy of calcium channel blockers support the view that calcium influx is an important step in initiating the contractile activity of uterine smooth muscle.