Effects of neuroleptics on 3H-haloperidol and 3H-cis(Z)-flupenthixol binding and on adenylate cyclase activity in vitro. |
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Authors: | J Hyttel |
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Affiliation: | Departments of Pharmacology and Neurobiology The University of Texas Medical School at Houston Houston, Texas 77030, USA |
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Abstract: | The subcellular localization of dopamine-sensitive adenylate cyclase was studied in rat brain striatum and compared to the distribution of dopamine binding sites. The highest specific activity of adenylate cyclase activities sensitive to dopamine was associated almost exclusively with synaptic membranes (mithchondrial fraction; P2). Using [3H] haloperidol and [3H] apomorphine as markers for the dopamine receptor, specific binding was observed in both the mitochondrial (P2) and microsomal (P3) fractions. Data for the mitochondrial fraction revealed a heterogeneity of binding sites. Two saturable sites for [3H] haloperidol were observed with Kd values of 2.5nM and 12.5nM respectively. Overall, the localization of multiple binding sites in the crude synaptosomal fraction correlates well with the localization of dopamine-sensitive adenylate cyclase in this fraction. |
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