Effect of acute administration of 1,2,3,4-tetrahydroisoquinoline on the levels of glutathione and reactive oxygen species, and on the enzymatic activity of gamma-glutamyl transpeptidase in dopaminergic structures of rat brain.

The effect of acute administration of 1,2,3,4-tetrahydroisoquinoline, an endogenous substance suspected of producing Parkinsonism in humans, on the levels of glutathione and reactive oxygen species and on the enzymatic activity of gamma-glutamyl transpeptidase was investigated in the substantia nigra, striatum and cortex of rat brain. Four hours after a single dose of 1,2,3,4-tetrahydroisoquinoline (100 mg/kg i.p.), a significant increase in tissue glutathione level was found in the dopaminergic structures studied. The most pronounced effect was observed in the substantia nigra and cortex, and the weakest in the striatum. At the same time, significant inhibition of gamma-glutamyl transpeptidase was observed in the substantia nigra, cortex and striatum whose extent strictly corresponded to the increase in glutathione levels in those structures. Moreover, in 1,2,3,4-tetrahydroisoquinoline-treated rats, the production of reactive oxygen species was significantly reduced in the substantia nigra, whereas it was markedly enhanced in the striatum.Our results suggest that the increase in tissue glutathione level in the dopaminergic structures studied results from inhibition of gamma-glutamyl transpeptidase and refers to the extracellular pool of this peptide. Moreover, it is likely that both the 1,2,3,4-tetrahydroisoquinoline-induced alterations in glutathione level and the enhanced production of reactive oxygen species in the striatum may have implications for the pathogenesis of Parkinson's disease.