On the Mechanism of Pancuronium‐induced Super‐sensitivityto Noradrenaline in Rat Smooth Muscle

Abstract

Pancuronium bromide (5 × 10−5m) caused super‐sensitivityto noradrenaline in the rat isolated vas deferens and hepatic portal vein. This super‐sensitivitywas manifest as a parallel leftward shift of the dose‐response curve for noradrenaline with no alteration of the maximum response to the agonist. Pancuronium did not potentiate the response of the vas and portal vein to St 91, anα‐adrenocep‐tor agonist which is not a substrate for Uptake x. Pancuronium did not potentiate the response of the vas to CaCl2. In vasa deferentia made supersensitive to noradrenaline by treatment with cocaine (1 × 10−5m) pancuronium induced no further potentiation of the response to noradrenaline. However, the super‐sensitivityto noradrenaline induced by pancuronium alone was augmented by the addition of cocaine. Histofluorescence studies showed that pancuronium inhibited neuronal uptake of α‐methyl noradrenaline in various noradrenergically‐innervated tissues from reserpine‐treated rats. This study, with support from the literature, suggests that pancuronium induces noradrenaline super‐sensitivityby blockade of Uptake!.

Non-Relaxant Properties of Neuromuscular Blocking Drugs

“…Several groups of workers have shown that pancuronium blocks noradrenaline reuptake into sympathetic nerve endings (Uptake 1) both in cardiac muscle and in smooth muscle of guineapigs and rats (Ivankovich et al, 1975;McGrath, 1977, 1978;Quintana, 1977;Marshall and Ojewole, 1979;Tomlinson, 1979;Salt, Barnes and Conway, 1980). Fazadinium also produces this effect, but tubocurarine, meto-curine and gallamine do not, and Org NC45 is considerably less effective than pancuronium in this respect (Marshall and Ojewole, 1979;Docherty and McGrath, 1980;Marshall, McGrath et al, 198,0).…”