Differential distribution in, and release from, sympathetic nerve endings of endogenous noradrenaline and recently...

Guinea-pig vasa deferentia or hypogastric nerve-vas deferens preparations, preincubated with pargyline (to irreversibly inhibit monoamine oxidase), were exposed to 2.3 mumol/l of unlabelled adrenaline or of 3H-7-(-)-noradrenaline in the presence of hydrocortisone (to inhibit extraneuronal uptake). The vasa deferentia were then mounted in perifusion chambers and subjected to transmural electrical stimulation, electrical stimulation of the nerve, depolarization by potassium (50 mmol/l), or addition of tyramine (40 mumol/l). The evoked overflow of tritium and of unlabelled catecholamines was expressed as a fraction of their tissue content. For all stimuli, the fractional release of the exogenous amines was higher than that of endogenous noradrenaline. Thus, recently incorporated amines are preferentially mobilized irrespective of the particular type of releasing mechanism or the chemical nature of the amine. In vasa deferentia which had been loaded with increasing amounts of adrenaline (by incubating the tissues with adrenaline at concentrations ranging from 0.6 to 160 mumol/l), the fractional release of adrenaline decreased and became closer to that of endogenous noradrenaline. Hence, the access of exogenous catecholamines to the deepest storage sites requires higher concentrations of amines than those needed to reach the more easily releasable pools. Light microscope autoradiographs obtained from slices of vasa deferentia previously loaded with 2.3 mumol/l 3H-(-)-noradrenaline showed that the outer layers were strongly labelled with silver grains whereas the inner layers were poorly marked. It is concluded that recently incorporated amines are preferentially stored in varicosities close to the surface of the tissue and, in comparison with endogenous noradrenaline, are preferentially released from sympathetically innervated organs.