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CHARACTERIZATION OF A DOPAMINE-SENSITIVE ADENYLATE CYCLASE IN THE RAT CAUDATE NUCLEUS
Authors:Yvonne C  Clement-Cormier  R G Parrish  G L Petzold  J W Kebabian  P Greengard
Institution:Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, U.S.A.
Abstract:Abstract— An adenylate cyclase present in the caudate nucleus of rat brain, which is selectively stimulated by low concentrations of dopamine, and which is believed to mediate dopaminergic synaptic transmission, has been characterized with respect to several properties. The parameters studied included temperature, pH, ATP concentration, Mg/ATP ratio, and metal ion specificity. The effects of other compounds, including EGTA, NaF and several guanosine nucleotides, were also tested on the dopa-mine-sensitive adenylate cyclase. In addition, the subcellular distribution of the enzyme was studied. The highest specific activity was found in subcellular fractions enriched in nerve endings. A half-maximal increase in the activity of the enzyme in a subcellular fraction occurred in the presence of 4 × 10−6 M dopamine. Fluphenazine, a dopamine antagonist, competitively inhibited the activity of the enzyme in this fraction, with a calculated inhibition constant ( Ki ) of 8 × 10−9M.
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