L-DOPA increases noradrenaline turnover in central and peripheral nervous systems.
The ability of L-3,4-dihydroxyphenylalanine (L-DOPA) to release noradrenaline (NA) from peripheral and CNS neurons was studied using isolated rat vas deferens and in vivo frontal cortex microdialysis. Application of L-DOPA (30 microM) to vas deferens increased basal NA efflux but not electrical field stimulation-evoked release of NA when the tissue was pretreated with an inhibitor of MAO-B (clorgyline 1 microM) or an inhibitor of MAO-A and MOA-B (AGN-1133 1 microM). No effect on NA efflux was seen when the tissue was treated with rasagiline (0.005 microM; selective inhibitor of MAO-B), but rasagiline, AGN-1133 and clorgyline increased basal efflux of dopamine (DA) following L-DOPA. In microdialysis experiments, systemic administration of L-DOPA/carbidopa combination (50/12 mg.kg(-1)) increased the efflux of 3,4-dihydroxyphenylglycol and 3-methoxy,4-hydroxyphenylglycol but reduced that of NA. Microdialysate levels of NA, however were increased following L-DOPA/carbidopa when desipramine (1 microM) was infused locally via the probe, or following systemic administration of yohimbine (2 mg.kg(-1)). The data are consistent with the hypothesis that administration of L-DOPA is followed by increased axoplasmatic levels of DA which release NA from storage sites into the free cytoplasmatic pool.
Dayan
Lior
L
Pharmacology Department, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Finberg
John P M
JP
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D007980:Levodopa; D009638:Norepinephrine