Mechanisms of the inotropic actions of MPTP and MPP+ on isolated atria of rat.

Besides having toxic actions, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPP+ (1-methyl-4-phenyl-pyridinium ion) produce the release of catecholamines in the peripheral and central nervous systems. This paper reports on the effects of MPTP and MPP+ on isolated left atria of rats and their mechanisms. MPP+ and MPTP produced a concentration-dependent positive inotropic effect. This action was blocked by propranolol and nomifensine; however, inhibition of monoamine oxidase had no effect on the response. In atria from reserpinized rats, the positive inotropic effect of MPTP was also blocked and a negative inotropic effect was unmasked which continued to increase in magnitude during wash. The negative inotropic effect was markedly reduced by superoxide dismutase and catalase. These results indicate that MPTP and MPP+ produce a catecholamine-mediated positive inotropic effect that is not MAO-dependent, unlike the toxic actions of MPTP. These results also suggest that MPTP may directly damage cardiac muscle by generating free radicals which might explain why high doses of MPTP are lethal to animals.