Histochemical and functional relationships of catecholamines in adrenergic nerve endings. I. Participation of granular vesicles.

Combined microfluorometric histochemical and electron microscopic studies of the hypogastric nerve-vas deferens preparation permitted a correlation of information relative to possible functional compartments of norepinephrine in peripheral adrenergic nerve endings. Administration of α-methyl- m -tyrosine (αMMT) to rats reduced norepinephrine content of the vas deferens to 20% of normal, caused a marked reduction of catecholamine fluorescence in adrenergic nerve fibers and reduced the proportion of granular vesicles from the 53 to 64% normally observed in electron micrographs to 6 to 11% of total nerve ending vesicles. These depleted preparations responded well to stimulation of the hypogastric nerve, but not to tyramine. Exposure of vasa deferentia from αMMT-treated rats to dopa or dopamine in vitro , in the presence of a decarboxylase and dopamine-β-oxidase inhibitor, failed to restore the electron density of nerve ending vesicles significantly. However, norepinephrine in vitro restored almost normal numbers of granular vesicles. This finding suggested that the relationship between granular vesicles and a storage form of norepinephrine postulated by many workers could be confirmed directly. Interpretation of pharmacologic responses of this preparation depends upon knowledge of the distribution of norepinephrine between the intravesicular and extravesicular compartments.