Purine-induced alterations of dopamine metabolism in rat pheochromocytoma PC12 cells

Studies with cerebrospinal fluid from subjects with Parkinson's disease sug gest that purine abnormalities may be present in this disorder. The effects of purines on dopamine metabolism have not been characterized, though aden osine is known to inhibit dopaminergic neurotransmission. In this study, do pamine, its precursor 3,4-dihydroxyphenylalanine (DOPA), and its degradatio n products 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (H VA) were measured in rat pheochromocytoma PC12 cells following 24-h incubat ion with 5, 50, and 500 mu M adenosine, adenine, guanosine, guanine, hypoxa nthine, xanthine, and uric acid. Incubation with adenosine increased DOPA, DOPAC, and HVA, while adenine treatment decreased DOPA. Guanosine (500 mu M ) decreased DOPA, dopamine, and DOPAC, while lower concentrations increased DOPAC and HVA. Incubation with guanine decreased dopamine, and xanthine de creased dopamine and DOPAC. Hypoxanthine and uric acid exerted minimal effe cts. These results indicate that purines exert a variety of effects on dopa mine metabolism. The influence of purine metabolism on the dopaminergic def icit in the Parkinsonian brain merits further investigation. (C) 2000 Elsev ier Science Inc.