Abstract
Adenylate cyclase and guanosine triphosphatase (GTPase) activities in response to dopamine (DA) were determined in membranes prepared from striata of mice treated with haloperidol for a period of 3 months. D 1- and D 2 receptor-mediated effects were investigated in the presence of 2 μM (−)-sulpiride and 0.1 μM SCH 23390, respectively. The drug treatment produced a 38% increase in the maximal inhibition of adenylate cyclase activity elicited by DA via D 2 receptors. D 1-mediated stimulation of adenylate cyclase was not affected. The enhanced D 2 inhibition of adenylate cyclase was associated with a 45% increase in the stimulatory response of GTPase activity via D 2 sites. These results indicate that D 2 receptors linked to inhibition of adenylate cyclase and to stimulation of GTPase become supersensitive following in vivo chronic blockade of DA receptors.
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