HISTOCHEMICAL AND FUNCTIONAL RELATIONSHIPS OF CATECHOLAMINES IN ADRENERGIC NERVE ENDINGS. II. EXTRAVESICULAR NOREPINEPHRINE

¹ Departments of Pharmacology and Pathology, Yale University School of Medicine, New Haven, Connecticut

Further studies of the subcellular distribution of norepinephrine within intact adrenergic nerve endings have been carried out by means of microfluorometric histochemical and electron-microscopic examination of the rat hypogastric nerve-vas deferens preparation. After depletion of endogenous norepinephrine by pretreatment with reserpine, vas deferens preparations were exposed to 1.0 µM reserpine for 3 hr in vitro, followed by a 15-min exposure to 0.1 mM norepinephrine, which did iiot restore either adrenergic fiber fluorescence or granular vesicles (intravesicular compartment). However, after reserpine plus 0.1 mM iproniazid in vitro, exogenous norepinephrine accumulated in the extravesicular compartment but did not enter the intravesicular compartment, as evidenced by return of adrenergic fiber fluorescence without restoration of the normal proportion of granular vesicles. The same effects were obtained with preparations from untreated rats, after exposure to reserpine for 6 hr in vitro. Tyramine, 0.1 mM, alone or with iproniazid, also depleted norepinephrine in vitro; exogenous norepinephrine added subsequently appeared to accumulate in the extravesicular compartment. Contractile activity of the hypogastric nerve-vas deferens preparation was inhibited by exogenous norepinephrine, under circumstances which favored accumulation of the amine in the extravesicular compartment, specifically: 1) depletion of endogenous, intravesicular norepinephrine, 2) addition of exogenous norepinephrine and 3) protection of extravesicular norepinephrine by inhibition of monoamine oxidase.