Effect of temperature and ionic environment on the specific binding of (3)H(-)sulpiride to membranes from different rat brain regions.
Sulpiride is an antipsychotic drug endowed with the properties of a dopamine antagonist. The failure of sulpiride to inhibit neostriatal dopamine stimulated adenylate cyclase activity indicated that this drug is a selective D(2) receptor antagonist. In this study we used a novel synthesized (2)H(-)sulpiride with very high specific activity (72 Ci/mol) and characterized the temperature sensitivity of the binding sites labeled by this compound. Kinetic analysis of (3)H(-)sulpiride binding in rat striatum showed unstable behavior when incubation was performed at 37 or 30 degrees C. However when experiments were carried out at 15 or 10 degrees C, binding reached a stable steady-state within 10 min. Scatchard analysis of binding isotherms obtained at 10 degrees C showed a 5-fold increase in the maximum number of binding sites and a decrease in K(d) values to one-third those obtained at 37 degrees C. Pharmacological characterization of the binding sites labeled by (3)H(-)sulpiride at 10 degrees C showed a greater affinity for antagonists but not for agonists than 37 degrees C. Under both experimental condition, (3)H(-)sulpiride binding sites were Na(+) and GTP-sensitive. The temperature sensitive binding phenomenon appeared to be area specific. (3)H(-)sulpiride binding sites in tissues other than from striatum were influenced less or not at all by changes in incubation temperature.
Carboni
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Institute of Pharmacology and Experimental Toxicology, University of Cagliari, Italy.
Memo
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Tanda
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Carruba
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Spano
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