AJP - Gastrointestinal and Liver Physiology, Vol 253, Issue 6 809-G815, Copyright © 1987 by American Physiological Society
Chronic alterations in jejunal myoelectric activity in rats due to MPTP
E. Y. Eaker, G. B. Bixler, A. J. Dunn, W. V. Moreshead and J. R. Mathias
Department of Medicine, College of Medicine, University of Florida, Gainesville 32610.
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.
