COMPARATIVE STUDY OF THE TOXIC EFFECT OF N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE AND DOPAMINE ON RAT BRAIN MITOCHONDRIA IN VITRO

AIM：To compare the toxic action of n-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP) and dopamine on rat brain mitochondria. METHODS: After coincubation of MPTP or dopamine with isolated rat brain mitochondria, the membrane fluidity, membrane potential, mitochondrial swelling, the activity of total ATPase and mitochondrial respiratory chain as well as the levels of H₂O₂,and malondialdehyde (MDA) were measured. RESULTS: Both MPTP and dopamine （1×10^-5～1×10^-3 mol.L^-1）　were shown to decrease mitochondrial membrane fluidity. MPTP decreased the mitochondrial membrane potential but did not induce swelling of mitochondria and decrease of total ATPase activity in mitochonria. Dopamine inhibited total ATPase activity and induced mitochondrial swelling but showed little effect on the membrane potential. Both compounds increased the MDA level. Dopamine enhanced both H₂O₂ and generation in the mitochondria. MPTP only increased H₂O₂ generation. Dopamine significantly inhibited the respiratory chain activity. MPTP showed slight stimulating effect on respiratory chain activity. CONCLUSION: MPTP itself exhibited toxic action on rat brain mitochondria. Some of its effects were different from those of dopamine. The toxic effect of both compounds was related to the increment in production of reactive oxygen species through different pathways.