Nigrostriatal catecholamine metabolism in guinea pigs is altered by purine enzyme inhibition

Abstract 

The effect of purine enzyme inhibition on catecholamine metabolism was investigated in guinea pigs. Catecholamine levels were measured in the nigrostriatal brain structures of male guinea pigs following treat- ment with allopurinol (a xanthine oxidase inhibitor; 250 mg/kg i.p.) or allantoxanimide (a uricase inhibitor; 200 mg/kg i.p.) once a day for 4 days. Tissue was analyzed from the striatum and the substantia nigra. Norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid, and uric acid were quantified with electrochemical and ultraviolet detection following separation by liquid chromatography. Allopurinol had no effect on nigrostriatal dopamine levels but decreased DOPAC levels (P<0.05) in the striatum. Allantoxanimide increased norepinephrine levels and decreased DOPAC levels in the striatum (P<0.05). Allopurinol decreased uric acid levels in the striatum and substantia nigra (P<0.05). Allantoxanimide increased uric acid levels in the striatum and the substantia nigra (P<0.05). These results indicate that alterations in purinergic enzyme activity can influence catecholamine metabolism within the nigrostriatal system of the guinea pig.