Effect of veratridine on the fluxes of 3H-noradrenaline and 3h-bretylium in the rat vas deferens in vitro.

Abstract

The effect of the depolarizing agent veratridine on the accumulation and release of of 3H-noradrenaline and 3H-bretylium in in the rat vas deferens in vitro was examined. Veratridine produced inhibition of the accumulation and induced marked release of the amines. In vas deferens from non-reserpinized rats the release of noradrenaline evoked by veratridine was partially antagonized by omission of Ca2+ in the incubation medium and partially inhibited by low concentrations of desipramine. In reserpinized vas deferens the release of noradrenaline like that of bretylium in normal vas was not affected by omission of Ca2+ but inhibited by low concentrations (3-5 X 10(-7) M) of desipramine. Tetrodotoxin and the local anesthetics millicaine and lidocaine antagonized the effect of veratridine on the accumulation and release of the amines, probably due to prevention of the depolarization. High concentration (3 X 10(-5) M) of desipramine had a similar effect on the release of noradrenaline in normal tissue in presence of external Ca2+. It is concluded that noradrenaline is released by veratridine from normal vas deferens by two mechanisms: 1) an exocytosis release, 2) a carrier mediated desipramine sensitive outward transport; In reserpinized tissue the second mechanism is solely responsible for the release of noradrenaline. Bretylium is only released by the second mechanism. It is suggested that the inhibiton of the amine accumulation by veratridine is due to an equilibrium of the influx at a low tissue to medium ratio.