Effects of the parkinsonism-inducing neurotoxin MPTP and its metabolite MPP+ on sympathetic adrenergic nerves in mouse iris and atrium.
The effect of systemic administration of the parkinsonism-inducing neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and its metabolite MPP+ (1-methyl-4-phenylpyridine) on sympathetic adrenergic nerves in mouse iris and atrium has been investigated employing histo- and neurochemical techniques. The results indicate that MPTP does not have any potent neurotoxic effects on sympathetic adrenergic nerves. The effects of MPTP noted appear mainly to be restricted to a noradrenaline (NA) -depleting action and an acutely transient impairment of the NA uptake mechanism. This latter effect could be counteracted by monoamine oxidase inhibition. MPP+ was found to have more potent neurotoxic actions than MPTP as reflected i.e. by a patchy loss of histochemically demonstrable adrenergic nerves in iris which persisted for at least 7 days. Pretreatment with the NA uptake blocker desipramine antagonised the effects of MPP+, indicating that neurotoxicity is mediated via the NA uptake mechanism. The difference in neurotoxic potency of MPTP between sympathetic adrenergic nerves and central catecholamine neurons might be related to differences in metabolism of MPTP in the CNS and the periphery and/or due to the sympathetic adrenergic nerves being more resistant towards the cytotoxic actions following MPTP administration.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D000320:Adrenergic Fibers / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D007498:Iris / Q000187:drug effects* / Q000294:innervation; D008297:Male; D051379:Mice; D009410:Nerve Degeneration / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D011725:Pyridines / Q000633:toxicity*; D011726:Pyridinium Compounds / Q000633:toxicity
D011725:Pyridines; D011726:Pyridinium Compounds; D010293:Pargyline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D003891:Desipramine; D009638:Norepinephrine