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Chronic alterations in jejunal myoelectric activity in rats due to MPTP
E Y Eaker1, G B Bixler, A J Dunn
1Department of Medicine, College of Medicine, University of Florida, Gainesville 32610.
Abstract:
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.
Insights
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes intestinal disruption in rats, potentially linked to Parkinson's disease. This effect was blocked by pargyline and reduced by Sinemet, suggesting an enteric nervous system cause.
Area of Science:
- Neuroscience
- Gastroenterology
- Pharmacology
Background:
- Parkinsonian patients exhibit symptoms resembling intestinal pseudo-obstruction.
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces Parkinsonism by damaging dopaminergic neurons.
- Rodent models show less severe catecholamine depletion compared to primates after MPTP exposure.
Purpose of the Study:
- To investigate the effects of MPTP on intestinal myoelectric activity in Wistar rats.
- To determine if MPTP-induced intestinal changes are mediated by central or enteric nervous system effects.
- To examine the potential protective roles of monoamine oxidase inhibitors and dopamine replacement therapy.
Main Methods:
- Chronic bipolar electrodes were used to monitor proximal jejunum myoelectric activity in rats.
- MPTP was administered to induce Parkinsonian-like symptoms and intestinal changes.
- Pargyline (monoamine oxidase inhibitor) and Sinemet (L-dopa and carbidopa) were used to assess their effects on myoelectric activity and dopamine levels.
Main Results:
- MPTP significantly disrupted migrating myoelectric complexes and prolonged irregular spike activity in the jejunum (P < 0.001).
- Pargyline pretreatment significantly blocked these MPTP-induced myoelectric changes.
- Sinemet administration decreased the severity of MPTP-induced myoelectric disruption.
- Jejunal dopamine levels decreased significantly after MPTP, but at higher doses than those affecting myoelectric activity.
Conclusions:
- MPTP induces significant intestinal myoelectric disruption in rats.
- This disruption appears to be mediated by enteric, not central, nervous system effects.
- Pharmacological interventions like pargyline and Sinemet can modulate MPTP-induced intestinal dysmotility.