Purine-induced alterations of dopamine metabolism in rat pheochromocytoma PC12 cells.
Studies with cerebrospinal fluid from subjects with Parkinson's disease suggest that purine abnormalities may be present in this disorder. The effects of purines on dopamine metabolism have not been characterized, though adenosine is known to inhibit dopaminergic neurotransmission. In this study, dopamine, its precursor 3,4-dihydroxyphenylalanine (DOPA), and its degradation products 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured in rat pheochromocytoma PC12 cells following 24-h incubation with 5, 50, and 500 microM adenosine, adenine, guanosine, guanine, hypoxanthine, xanthine, and uric acid. Incubation with adenosine increased DOPA, DOPAC, and HVA, while adenine treatment decreased DOPA. Guanosine (500 microM) decreased DOPA, dopamine, and DOPAC, while lower concentrations increased DOPAC and HVA. Incubation with guanine decreased dopamine, and xanthine decreased dopamine and DOPAC. Hypoxanthine and uric acid exerted minimal effects. These results indicate that purines exert a variety of effects on dopamine metabolism. The influence of purine metabolism on the dopaminergic deficit in the Parkinsonian brain merits further investigation.
Loeffler
D A
DA
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI, USA.
Camp
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DM
Juneau
P L
PL
Harel
E
E
LeWitt
P A
PA
D000225:Adenine / Q000378:metabolism / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D006147:Guanine / Q000378:metabolism / Q000494:pharmacology; D006151:Guanosine / Q000378:metabolism / Q000494:pharmacology; D019271:Hypoxanthine / Q000378:metabolism / Q000494:pharmacology; D017072:Neostriatum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011687:Purines / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014527:Uric Acid / Q000378:metabolism / Q000494:pharmacology; D019820:Xanthine / Q000378:metabolism / Q000494:pharmacology
D011687:Purines; D006151:Guanosine; D019820:Xanthine; D014527:Uric Acid; D019271:Hypoxanthine; D006147:Guanine; D000225:Adenine; D000241:Adenosine; D004298:Dopamine