D1 dopamine receptors in the rat retina: effect of dark adaptation and chronic blockade by SCH 23390.

Chronic administration of SCH 23390 (0.03 mg/kg s.c., three times daily), a selective D1 dopamine (DA) receptor blocker, markedly increased the [3H]SCH 23390 binding in the rat retina. As revealed by the Scatchard plot analysis of saturation data from retinal homogenates, chronic SCH 23390 increased the total number of binding sites by 34% when compared to tissue from solvent-treated rats but failed to change the apparent affinity of [3H]SCH 23390 for its binding sites. The up-regulation of [3H]SCH 23390 binding sites was paralleled by an increase in the sensitivity of retina DA-sensitive adenylate cyclase. In fact, DA (5 X 10(-6) M to 10(-4) M) produced a higher accumulation of cyclic AMP (from 58 to 128%) in the retina of SCH 23390-treated rats as compared to the accumulation (from 35 to 80%) found in tissue from solvent-treated rats. Since dark adaptation decreases dopaminergic function in the rat retina, the influence of environmental lighting on [3H]SCH 23390 binding and DA-sensitive adenylate cyclase activity was studied. After 4 h of dark adaptation the density of [3H]SCH 23390 binding sites was higher (32%) than that from light-adapted rats. On the other hand, dark adaptation failed to change the apparent affinity of [3H]SCH 23390 for its binding sites. Moreover, DA elicited a greater stimulation of adenylate cyclase activity in homogenates of retina from dark-adapted rats. Thus, the maximum adenylate cyclase response to DA resulted higher in the retina of dark-adapted rats (152%) than that found in the retina of light-adapted animals (97%).(ABSTRACT TRUNCATED AT 250 WORDS)