Neuronal re-uptake of noradrenaline by sympathetic nerves in humans.
1. Plasma concentrations of [3H]dihydroxyphenylglycol, the intraneuronal metabolite of noradrenaline, were examined during intravenous infusion of [3H]noradrenaline in 43 subjects, to assess the nature of its formation. Noradrenaline re-uptake by sympathetic nerves was estimated in 11 subjects from the effects of neuronal uptake blockade with desipramine on noradrenaline clearance and plasma concentrations of [3H]dihydroxyphenylglycol and endogenous dihydroxyphenylglycol. In seven subjects noradrenaline re-uptake and spillover into plasma were examined before and during mental arithmetic or handgrip exercise. 2. During infusion of [3H]noradrenaline, plasma [3H]dihydroxyphenylglycol increased progressively, indicating its formation from previously stored [3H]noradrenaline leaking from vesicles as well as from [3H]noradrenaline metabolism immediately after removal into sympathetic nerves. Thus, to estimate noradrenaline re-uptake, the amount of [3H]dihydroxyphenylglycol derived from [3H]noradrenaline metabolized immediately after removal into the sympathetic axoplasm must be isolated from that derived from [3H]noradrenaline sequestered into vesicles. 3. At rest in the supine position the rate of noradrenaline re-uptake was 474 +/- 122 pmol min-1 kg-1, 9.5-fold higher than the rate of spillover of noradrenaline into plasma (49.6 +/- 6.4 pmol min-1 kg-1). Noradrenaline re-uptake and spillover into plasma were both increased during mental arithmetic and isometric handgrip exercise.
Eisenhofer
G
G
Baker Medical Research Institute, Prahran, Victoria, Australia.
Esler
M D
MD
Meredith
I T
IT
Ferrier
C
C
Lambert
G
G
Jennings
G
G
D000328:Adult; D003891:Desipramine / Q000494:pharmacology; D015444:Exercise / Q000502:physiology; D006801:Humans; D008297:Male; D008606:Mental Processes / Q000502:physiology; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000097:blood; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000008:administration & dosage / Q000378:metabolism*; D011849:Radioactive Tracers; D013564:Sympathetic Nervous System / Q000378:metabolism*; D014316:Tritium
D011849:Radioactive Tracers; D014316:Tritium; D008734:Methoxyhydroxyphenylglycol; D003891:Desipramine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine