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

• Published in: Brain research bulletin Vol. 52; no. 6; pp. 553 - 558
• Main Authors: Loeffler, D.A, Camp, D.M, Juneau, P.L, Harel, E, LeWitt, P.A
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2000; Elsevier Science
• Subjects: Adenine - metabolism; Adenine - pharmacology; Adenosine - metabolism; Adenosine - pharmacology; Animals; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Dopamine; Dopamine - metabolism; Guanine - metabolism; Guanine - pharmacology; Guanosine - metabolism; Guanosine - pharmacology; Hypoxanthine - metabolism; Hypoxanthine - pharmacology; Medical sciences; Neostriatum - metabolism; Neostriatum - pathology; Neostriatum - physiopathology; Neural Pathways - metabolism; Neural Pathways - pathology; Neural Pathways - physiopathology; Neurology; Neurons - metabolism; Neurons - pathology; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson Disease - physiopathology; Parkinson’s disease; PC12; PC12 Cells - drug effects; PC12 Cells - metabolism; Purines; Purines - metabolism; Purines - pharmacology; Rats; Substantia Nigra - metabolism; Substantia Nigra - pathology; Substantia Nigra - physiopathology; Uric Acid - metabolism; Uric Acid - pharmacology; Xanthine - metabolism; Xanthine - pharmacology; PC12; Purines; Dopamine; Parkinson’s disease; Nervous system diseases; Rat; Rodentia; Parkinson disease; Catecholamine; Metabolism; In vitro; Cerebral disorder; Vertebrata; Mammalia; Cell line; Neuron; Animal; Central nervous system disease; Neurotransmitter; Degenerative disease; Purine; Extrapyramidal syndrome
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/S0361-9230(00)00293-8

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 μM adenosine, adenine, guanosine, guanine, hypoxanthine, xanthine, and uric acid. Incubation with adenosine increased DOPA, DOPAC, and HVA, while adenine treatment decreased DOPA. Guanosine (500 μM) 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.