DISTRIBUTION OF H-3-(+ OR -) NORADRENALINE IN RABBIT AORTIC STRIPS AFTER INHIBITION OF NORADRENALINE-METABOLIZING ENZYMES

Rabbit aortic strips (nerve-free, reserpine-pretreated or normal) whose noradrenaline-metabolizing enzymes [monoamineoxidase and catechol-0-methyltransferase] were inhibited (by in vitro treatment with 0.5 mM pargyline for 30 min and by the presence of 0.1 mM U-0521) 3'',4''-dihydroxy-2-methylpropiophenone were exposed to 1.18 .mu.M 3H-(.+-.)noradrenaline for 30 min (in most experiments). At the end of the incubation some strips were used for analysis of radioactivity (i.e., of noradrenaline and its metabolites), while for others the efflux of radioactivity was determined during 240 min of wash out with amine-free solution. An estimate of the original distribution of the amine into the various extraneuronal and neuronal compartments of the tissue was obtained by compartmental analysis of the efflux curves. Extracellular amine distributes into "compartment I + II" (characterized by a half time for efflux of > 1 min); compartment size and half time for efflux were similar to those obtained for 14C-sorbitol. The extraneuronal accumulation of noradrenaline is a quickly equilibrating process which involves compartments III and IV (with half times for efflux of 3 and 11 min, respectively). Compartment IV represents not only extraneuronally but also neuronally distributed noradrenaline. The neuronal accumulation of noradrenaline is a slowly equilibrating process which can be subdivided into axoplasmic and vesicular accumulation. The axoplasmic accumulation of noradrenaline is associated with compartments IV and V (the latter characterized by a half time for efflux of 95 min). The half time of the efflux from compartment V was independent of the original filling of this compartment (the degree of filling have been varied by changes in the duration and the amine concentration of the incubation). The vesicular accumulation of noradrenaline resulted in the appearance of a "bound fraction" (i.e., of amine not participating in the efflux determined during 240 min of wash out) and in an increase in the half time of the efflux from compartment V. The rate of relaxation (of strips initially exposed to noradrenaline and then washed out) was apparently affected by the efflux of unchanged amine from extraneuronal and neuronal stores.