Alpha-adrenergic modulation of glutathione metabolism in isolated rat hepatocytes.

Glutathione metabolism was studied in isolated hepatocytes from 48-h starved rats. Phenylephrine (10 microM, final concentration) was incubated in the presence of a mixture of L-glutamine, glycine, L-serine, and L-methionine (at 10 times their normal plasma concentration). Alpha-adrenergic stimulation provoked a decrease in glutathione (GSH) synthesis. This effect was accompanied by an enhanced efflux of glutathione from the cells. Phenylephrine stimulated the rate of glutathione disulfide (GSSG) formation; however, this effect was clearly insufficient to explain the disappearance of GSH. Our results suggest that the decrease in cellular GSH levels observed under conditions of shock, stress…