Production and disposition of 1-methyl-4-phenylpyridinium in primary cultures of mouse astrocytes.

摘要: Dopaminergic neurons are a primary target for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity. However, the conversion of MPTP to its neurotoxic 1-methyl-4-phenylpyridinium metabolite (MPP+) is likely occur in astrocytes via monoamine oxidase (MAO)-dependent formation 1-methyl-4-phenyl-2,3-dihydropyridinium intermediate (MPDP+). The main purpose this study was characterize molecular mechanism(s) by which MPP+, once generated astrocytes, may reach extracellular space become available active accumulation into dopaminergic neurons. Primary cultures mouse were used as an vitro model system. After addition MPTP, levels MPP+ found increase at constant rates both intracellularly and extracellularly time points when no sign cytotoxicity evident. In contrast, MPDP+ remained quite stable during 4 days incubation presence MPTP. Finally, allowed accumulate pretreatment with either or then incubated fresh medium not containing intracellular rapidly declined corresponding amounts compound medium. Results compatible following conclusions: 1) accumulated compartment incubations released from consequence own cytotoxic effects; 2) can be formed presumably autoxidation after latter has been within crossed astrocyte membranes; 3) despite charged chemical structure, cross plasma membrane toward being astrocytes.