Increases in [H-3]FK-506 and [H-3]L-N-G-nitro-arginine binding in the rat brain after nigrostriatal dopaminergic denervation

Receptor autoradiographic technique was studied to investigate sequential c hanges in FK-506 binding proteins, nitric oxide synthase and dopamine uptak e sites in the brain 1 week to 8 weeks after unilateral 6-hydroxydopamine i njection of the medial forebrain bundle in rats. [H-3]FK-506, [H-3]L-N-G-ni tro-arginine and [H-3]mazindol were used to label FK-506 binding proteins ( immunophilin), nitric oxide synthase and dopamine uptake sites, respectivel y. [H-3]FK-506 binding showed about 13-25% increase in the ipsilateral stri atum from 2 to 8 weeks after degeneration of nigrostriatal pathway. However , no significant change in [H-3]FK-506 binding was observed in the ipsilate ral substantia nigra during the postlesion periods. In the contralateral si de, [H-3]FK-506 binding also showed about 13-25% increase in the striatum f rom 2 to 8 weeks postlesion. The substantia nigra showed a 21% increase in [H-3]FK-506 binding only 2 weeks after the lesioning. On the other hand, [H -3]L-N-G-nitro-arginine binding showed about 21-31% increase in the parieta l cortex and striatum I week or 2 weeks postlesion. In the contralateral si de, a 21% increase in [H-3]L-N-G-nitro-arginine binding was found in the do rsolateral striatum only 1 week postlesion. In contrast, degeneration of ni grostriatal pathway caused a conspicuous loss of [H-3]mazindol binding in t he ipsilateral striatum (87-96%), substantia nigra (36-73%) and ventral teg mental area (91-100%) during the postlesion periods. In the contralateral s ide, no significant changes in [H-3]mazindol binding were observed in these areas upto 8 weeks after the postlesion. The present study demonstrates th at unilateral injection of 6-hydroxydopamine into the medial forebrain bund le of rats can cause a significant increase in [H-3]FK-506 and [H-3]L-N-G-n itro-arginine bindings in the brains. In contrast, a marked reduction in [H -3]mazindol binding is observed in the brains after the lesioning, indicati ng severe damage to nigrostriatal dopaminergic pathway. These results sugge st that immunophilin and nitric oxide synthase may play some role in the pa thogenesis of neurodegenerative disorders such as Parkinson's disease.