On the mechanism of the accumulation of 3H-bretylium in peripheral sympathetic nerves.

The uptake of bretylium-(N-3H-methyl) iodide in the rat heart atrium in vitro was examined. The uptake was linear for at least 1 hr and was strongly inhibited by (+)-amphetamine, (-)-noradrenaline, desipramine, cocaine, DSP 4 [N-(2-bromobenzyl)-N-(2-chloroethyl)ethylamine hydrochloride], guanethidine and ouabain. The amphetamine sensitive part of the uptake was almost completely abolished by pre-treatment of the rats with 6-hydroxydopamine and was dependent on the presence of sodium ions. Reserpine had no effect. (+)-Amphetamine but not desipramine caused an increase of the efflux of bretylium from the tissue. The apparent Km value of the active bretylium uptake was 3 x 10(-6) M, which was 10 times higher than that of the uptake of (-)-noradrenaline in the rat heart atrium (Km = 3 x 10(-7) M). The inhibition constants (Ki) for bretylium in inhibiting the noradrenaline uptake and for (-)-noradrenaline in inhibiting the bretylium uptake were 7 x 10(-6) M and 4 x 10(-7) M, respectively. The results obtained support the hypothesis that bretylium is taken up by the same mechanism as that carrying noradrenaline into the nerve terminals but is not bound in the noradrenaline storage vesicles.