Parkinsonism-inducing neurotoxin N-methyl-4-phenyl-1236 -tetrahydropyridine: characterization and localization of receptor binding sites in rat and human brain.

摘要

N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces neuropathologic and clinical abnormalities in humans and animals that closely resemble idiopathic Parkinson disease. [3H]MPTP binds with high affinity (Kd = 28 X 10(-9) M) to brain membranes. The chemical specificity of the binding sites corresponds to structure-activity requirements for neurotoxicity. Autoradiographic studies in human brain show very high receptor densities in the caudate, substantia nigra, and locus coeruleus, which may explain the neurotoxic and neurochemical sequelae of MPTP administration. In contrast to the human, rat substantia nigra and caudate display only moderate receptor concentrations. This species difference may explain the difficulty in producing selective nigrostriatal degeneration in rats. Sites densely labeled in rat brain include the locus coeruleus, interpeduncular nucleus, arcuate and periventricular hypothalamic nuclei, and the subfornical organ.