Control of the neurotoxicity of 6-hydroxydopamine by intraneuronal noradrenaline in rat iris.
In vitro studies with the neurotoxic compounds 6-hydroxydopamine (6-OH-DA) and 6-aminodopamine (6-A-DA) showed that noradrenaline (NA) markedly inhibited the autooxidation of 6-OH-DA, but not of 6-A-DA. In vivo studies of the adrenergic nerves in rat iris showed that the neurotoxic potency of 6-OH-DA, but not 6-A-DA, was increased after NA depletion by alpha-methyl-p-tyrosine methylester (H44/68). Neurotoxicity was evaluated by measuring the associated decrease in 3-H-NA uptake. Intraocular injection of NA counteracted the degenerative action of 6-OH-DA in both untreated and H44/68 pretreated rats. Intraocular NA did not interfere with the neurotoxicity of 6-A-DA. Additionally, octopamine did not affect the rate of autooxidation nor the neurotoxic potency of 6-OH-DA or 6-A-DA. Control experiments with 3-H-6-OH-DA showed that the intraneuronal NA levels did not significantly affect the intraneuronal accumulation of 6-OH-DA. The parallelism between the in vitro results on autooxidation and in vivo data on neurotoxicity makes it appear that the neurotoxic potency of 6-OH-DA and 6-A-DA is closely associated with their rates of autooxidation. The control of the degenerative action of 6-OH-DA by intraneuronal NA may be mediated via reaction of NA with radicals formed from oxygen during autooxidation of 6-OH-DA.
D000818:Animals; D003864:Depression, Chemical; D004298:Dopamine / Q000378:metabolism*; D006892:Hydroxydopamines / Q000378:metabolism; D007498:Iris / Q000378:metabolism*; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology*; D009655:Octopamine / Q000494:pharmacology; D010101:Oxygen Consumption; D051381:Rats; D013997:Time Factors
D006892:Hydroxydopamines; D008781:Methyltyrosines; D009655:Octopamine; D004298:Dopamine; D009638:Norepinephrine