Plasma dihydroxyphenylglycol for estimation of noradrenaline neuronal re-uptake in the sympathetic nervous system in vivo.
1. Neuronal re-uptake is the primary means for terminating the actions of endogenously released noradrenaline. A portion of the recaptured noradrenaline is deaminated to form dihydroxyphenylglycol. The present report describes a technique using plasma dihydroxyphenylglycol for estimation of the rate of neuronal reuptake of endogenous noradrenaline in vivo. 2. 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: (i) 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. 3. 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). 4. 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 (less than 9%) of the noradrenaline released into the synaptic cleft spills over into the circulation.
Eisenhofer
G
G
Clinical Neuroscience Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland.
Goldstein
D S
DS
Kopin
I J
IJ
D000818:Animals; D003010:Clorgyline / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood; D006018:Glycols / Q000097:blood*; D007700:Kinetics; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D013564:Sympathetic Nervous System / Q000378:metabolism*
D006018:Glycols; D008734:Methoxyhydroxyphenylglycol; D003010:Clorgyline; D003891:Desipramine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D004837:Epinephrine