Chronic alterations in jejunal myoelectric activity in rats due to MPTP.
Parkinsonian patients may have symptoms consistent with intestinal pseudo-obstruction, but a primary intestinal abnormality has not been shown. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), after conversion to a toxic metabolite via the monoamine oxidase system, can induce Parkinson's disease by destroying dopaminergic neurons in the substantia nigra in humans and primates. Rodents have some catecholamine depletion but much less so than primates. Using chronic bipolar electrodes on the proximal jejunum of Wistar rats, we show significant, chronic migrating myoelectric complex disruption (P less than 0.001) and prolongation of irregular spike activity (P less than 0.001). Pargyline (a monoamine oxidase inhibitor) pretreatment significantly blocked these myoelectric changes. Sinemet (L-dopa and carbidopa), given after MPTP to replete dopamine, decreased the MPTP-induced migrating myoelectric complex disruption. Jejunal myenteric plexus dopamine levels were significantly decreased (to 61% of control) after MPTP but after much higher doses than were required to disrupt migrating myoelectric complex activity (180 mg/kg total vs. 30 mg/kg). Dopamine in the central nervous system was not depleted. We conclude that MPTP causes intestinal myoelectric disruption (which can be blocked by pargyline and decreased by Sinemet) possibly through enteric, but not central, nervous system effects.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002421:Caudate Nucleus / Q000378:metabolism; D004576:Electromyography; D004594:Electrophysiology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007082:Ileum / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects* / Q000502:physiology; D010293:Pargyline / Q000494:pharmacology; D010300:Parkinson Disease / Q000503:physiopathology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D013378:Substantia Nigra / Q000378:metabolism
D002395:Catecholamines; D011725:Pyridines; D010293:Pargyline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine