Functional recovery of D1 dopamine receptor-mediated stimulation of rat striatal adenylate cyclase activity following irreversible receptor modification by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ): evidence for spare receptors

Abstract

We report here the functional relationship between the time-dependent recovery of [3H]SCH 23390-labeled D1 dopamine receptors and the D1 receptor-mediated stimulation of rat striatal adenylate cyclase activity following irreversible receptor modification by in vivo administration of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline. Initial decreases in receptor density (-93%) and receptor-mediated enzyme activity (-78%) were accomplished without concomitant changes in guanosine triphosphate or forskolin-stimulated enzyme activity. The percentage of maximal D1 receptor-mediated enzyme activity was significantly greater than that of D1 receptor density at all recovery times. Dopamine-stimulated enzyme activity returned to control values by day 4, although D1 receptor density remained significantly below control levels at this time. No differences in the EC50's for dopamine stimulation of enzyme activity were observed at any of the recovery times. These data demonstrate that the stoichiometric relationship between the recovering D1 dopamine receptors and D1 receptor-mediated enzyme activity is not one to one, providing evidence for the presence of 'spare' D1 dopamine receptors in rat striatum.