Selective blockade of dopamine D-1 receptor by SCH 23390 affects dopamine agonist binding to 3H-spiperone labeled D-2 receptors in rat striatum.

Abstract

This study investigated the effects of selective blockade of dopamine D-1 receptors by SCH 23390 and selective stimulation of the receptors by SKF 38393 on the binding characteristics of 3H-spiperone labeled D-2 receptors in rat striatum. Selective blockade of D-1 receptors by 50 nM SCH 23390 significantly decreased the affinity of dopamine agonist for 3H-spiperone labeled D-2 receptors, but did not influence dopamine antagonist binding to D-2 receptors. Selective stimulation of D-1 receptors by SKF 38393 (100 nM) did not affect either dopamine agonist or antagonist binding to D-2 receptors. The characteristics of the effect of SCH 23390 on dopamine agonist binding to D-2 receptors was similar to those of GTP, but different from those of sodium ion. This effect could not be due to a direct modification of D-2 receptors by SCH 23390. Pertussis toxin (IAP) treatment significantly decreased the affinity of dopamine agonist for D-2 receptors and reduced the abilities of both SCH 23390 and GTP to decrease the affinity of dopamine agonist for D-2 receptors. These results suggest, therefore, putative interregulatory mechanism between dopamine D-1 and D-2 receptors and the possible involvement of a pertussis toxin sensitive protein in this mechanism.