Disposition of norepinephrine during nerve stimulation in dog saphenous vein

The relative importance of neuronal and extraneuronal uptake in the disposition of norepinephrine (NE) released by electrical stimulation (ES) from adrenergic nerves in isolated dog saphenous vein was determined. Helical strips of vein were incubated in L-[7-(3)H]NE (1 x 10(-6)M) and mounted for superfusion. Superfusate was collected continuously before, during, and after ES (10 V; 2 ms; 1, 2, and 5 Hz). Measurements were made of [3H]NE and its metabolites in vein and in superfusate. Previous studies have established that 3,4-dihydroxyphenylglycol (DOPEG) is of neuronal origin and O-methylated metabolites (OMM) are of extraneuronal origin. Thus, extraneuronal uptake was estimated directly by measuring the amounts of OMM in superfusate, and neuronal uptake followed by metabolism was estimated by measuring [3H]DOPEG. The magnitude of the neuronal uptake fraction that enters vesicles for reuse was estimated from the compensatory increases in [3H]NE and in OMM when neuronal uptake was blocked. Similar amounts of released NE were taken up by neuronal uptake, by extraneuronal uptake, and diffused out of the synaptic cleft. Between 5-20% of the released NE was sequestered in vesicles for reuse.