On the mechanism of pancuronium-induced supersensitivity to noradrenaline in rat smooth muscle.

1. Pancuronium bromide (5 x 10(-5) M) caused supersensitivity to noradrenaline in the rat isolated vas deferens and hepatic portal vein. This supersensitivity was manifest as a parallel leftward shift of the dose-response curve for noradrenaline with no alteration of the maximum response to the agonist. 2. Pancuronium did not potentiate the response of the vas and portal vein to St 91, an alpha-adrenoceptor agonist which is not a substrate for Uptake1. 3. Pancuronium did not potentiate the response of the vas to CaCl2. 4. In vasa deferentia made supersensitive to noradrenaline by treatment with cocaine (1 x 10(-5) M) pancuronium induced no further potentiation of the response to noradrenaline. However, the supersensitivity to noradrenaline induced by pancuronium alone was augmented by the addition of cocaine. 5. Histofluorescence studies showed that pancuronium inhibited neuronal uptake of alpha-methyl noradrenaline in various noradrenergically-innervated tissues from reserpine-treated rats. 6. This study, with support from the literature, suggests that pancuronium induces noradrenaline supersensitivity by blockade of Uptake1.