Influence of the frequency of nerve stimulation on the metabolism of ³H norepinephrine released from the perfused cat spleen: differences observed during and after the period of stimulation

The metabolism of ³H norepinephrine (³H NE) released by different frequencies of nerve stimulation was studied in the perfused cat spleen after labeling the endogenous stores with (-) ³H NE. For a wide range of frequencies of stimulation, unmetabolized ³H NE represented between 50 and 60% of the total increase in outflow of radioactivity elicited by nerve stimulation. The deaminated glycol, 3,4 dihydroxyphenylglycol (³H DOPEG), was the main metabolite of ³H NE released by nerve stimulation. When the increase in outflow of radioactivity was analyzed for the samples collected during nerve stimulation, there was a progressive decrease in the fraction of ³H NE released which was collected as ³H metabolites as the frequency of stimulation was increased from 0.5 to 5 Hz. For the samples collected in the poststimulation period, there was no frequency dependence in the metabolism of the released transmitter: approximately 75% of the total overflow of radioactivity was accounted for by the ³H NE metabolites, particularly ³H DOPEG. The time course of the metabolism of ³H NE released by nerve stimulation revealed that ³H DOPEG formation was rather small during stimulation and that it increased sharply in the poststimulation samples. The selective increase in ³H DOPEG formation in the poststimulation period is compatible with the view that neuronal uptake of the released transmitter might be increased immediately after nerve stimulation. Inhibition of neuronal uptake by cocaine or phenoxybenzamine prevented ³H DOPEG formation from ³H NE released by nerve stimulation. Yet, in the presence of cocaine, the fractional release of total radioactivity per shock was not increased at either 1, 5 or 30 Hz.