Distribution of 1-(3H)-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (3H-MPTP) in the frog: uptake in neuromelanin.
The nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes selective destruction of pigmented monoaminergic neurons of the brain, mainly in the substantia nigra. Primates and amphibians, whose nerve cells contain melanin, have shown a higher sensitivity for the toxic effects of MPTP than species which are lacking neuromelanin, e.g. rodents. In the present study the distribution after intraperitoneal injection of 3H-MPTP in frogs (Rana temporaria) was studied by whole-body autoradiography. Histochemical staining methods for melanin were used in order to identify the pigment in various tissues. Melanin-containing nerve cells were present bilaterally in the ventral motor parts of the frog brain. Melanin was also found in the meninges, around the cerebral ventricles and the aqueducts, and in the eyes, skin and liver. The results from the autoradiographic study of 3H-MPTP revealed a high accumulation and retention in all melanin-containing structures up to 15 days after administration (the longest survival time). The pigmented tissues showed the highest concentration of radioactivity in the body at all survival times. The MPTP-induced destruction of pigmented nerve cells may be related to the binding and storage of MPTP and/or its metabolites in neuromelanin, causing toxic cytoplasmic concentrations through the continuous release of substance from the melanin depot.
Sokolowski
A L
AL
National Board of Health and Welfare, Department of Drugs, Uppsala, Sweden.
Larsson
B S
BS
Lindquist
N G
NG
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000493:pharmacokinetics*; D000818:Animals; D001345:Autoradiography; D002490:Central Nervous System / Q000378:metabolism; D006651:Histocytochemistry; D008543:Melanins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011896:Rana temporaria; D014018:Tissue Distribution; D014316:Tritium
D008543:Melanins; C014121:neuromelanin; D014316:Tritium; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine