Dihydroxyphenylglycol as an index of neuronal uptake in dog saphenous vein.

Dihydroxyphenylglycol (DOPEG), the metabolite of norepinephrine (NE) that arises intraneuronally, was measured together with NE in superfusates collected before, during, and after nerve stimulation and in extracts of dog saphenous vein after superfusion and electrical stimulation (ES). Different concentrations of NE in the synaptic clefts were achieved by treating tissues with corticosterone, corticosterone and yohimbine, corticosterone and cocaine, or by omitting drugs from the superfusate. NE and DOPEG were quantitated by liquid chromatography with electrochemical detection. The time courses of NE overflow and DOPEG efflux into superfusate were followed. The amounts of DOPEG in superfusates under basal conditions were two to four times higher than the amounts of NE and progressively increased during ES except in tissues with neuronal uptake inhibited. NE overflow reached a steady state within the first 6 min of ES. Increased NE concentrations in synaptic clefts resulted in increased DOPEG production except where neuronal uptake was inhibited. The increased DOPEG production during ES appears to reflect the increased rate of neuronal uptake, which results in more NE being available for intraneuronal metabolism. No evidence was found that newly formed DOPEG was delayed in leaving the tissue. Thus the increase in DOPEG production that occurs during ES may be useful as an index of neuronal uptake of NE in dog saphenous vein.