Modulation of the concentration of noradrenaline at the neuro-effector junction in human saphenous vein.
We studied the importance of neuronal and extraneuronal uptake and of the pre-junctional alpha-adrenergic feed-back mechanism for the junctional noradrenaline concentration in the human saphenous vein. All major metabolites of the enzymatic breakdown of noradrenaline were detected in the overflow of superfused veins loaded with [3H]-noradrenaline. The efflux of 3,4-dihydroxyphenylglycol (DOPEG) was drastically reduced in preparations labelled after neuronal uptake blockade indicating its neuronal origin; the other metabolites are formed extraneuronally since they behaved distinctly differently from DOPEG under several experimental conditions. Extraneuronal uptake followed by enzymatic breakdown removes the same amount of noradrenaline from the biophase during nerve activity as that diffusing intact out of the tissue, whereas neuronal uptake appears only half as effective since the overflow of intact noradrenaline increases by only 48% in the presence of desmethylimipramine (DMI). However, in preparations mounted for isometric tension recording, neuronal uptake blockade potentiated contractions to alpha-adrenergic activation, emphasizing the functional importance of the neuronal disposition mechanism. By contrast, no evidence was found for a hydrocortisone-sensitive extraneuronal uptake compartment, suggesting that extraneuronal removal may have little, if any, functional importance. During nerve stimulation, yohimbine increased the amount of labelled noradrenaline present in the superfusate, while exogenously added noradrenaline decreased it in the presence of cocaine. Thus, prejunctional alpha-adrenoceptors can modulate the junctional concentration of neurotransmitter in the human saphenous vein.
D000328:Adult; D000368:Aged; D003042:Cocaine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D012501:Saphenous Vein / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha; D008734:Methoxyhydroxyphenylglycol; D003042:Cocaine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine