Plasma dihydroxyphenylglycol for estimation of noradrenaline neuronal re-uptake in the sympathetic nervous system in vivo

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Abstract
Neuronal re-uptake is the primary means for terminating the actions of endogenously released noradrenaline. A portion of the recaptured noradrenaline is deamineated to form dihydroxyphenylglycol. The present report describes a technique using plasma dihydroxyphenylglycol for estimation of the rate of neuronal re-uptake of endogenous noradrenaline in vivo. Neuronal re-uptake of noradrenaline in the sympathetic nervous system of the rat was estimated from the effects of neuronal uptake blockade with desipramine on three variables: (1) the plasma clearance of intravenously infused 3H-labelled noradrenaline, (ii) the plasma concentration of endogenous dihydroxyphenylglycol, and (iii) the plasma concentration of 3H-labelled dihydroxyphenylglycol formed from infused 3H-labelled noradrenaline. Desipramine decreased plasma dihydroxyphenylglycol by 36%, this representing the fraction of dihydroxyphenylglycol in plasma that was derived from recaptured noradrenaline. After desipramine, the decrease in the rate of neuronal uptake of 3H-labelled noradrenaline was 9.7 times that of the decrease in the plasma spillover of 3H-labelled dihydroxyphenylglycol. Since the appearances in plasma of dihydroxyphenylglycol from unlabelled and 3H-labelled noradrenaline were similar, the neuronal re-uptake of endogenous noradrenaline could be assumed to be 9.7 times as much as the plasma spillover of dihydroxyphenylglycol that was derived from recaptured noradrenaline (0.15 nmol min-1 kg-1). The rate of neuronal re-uptake of endogenous noradrenaline was estimated to be 1.45 nmol min-1 kg-1, whereas the plasma spillover of noradrenaline was 0.127 nmol min-1 kg-1. Thus, only a small fraction (< 9%) of the noradrenaline released into the synaptic cleft spills over into the circulation.