Dopamine receptors in the proximal tubule of the rabbit

Abstract

Dopamine receptors in glomeruli and tubular homogenates were characterized. Since the heterogeneity of kidney homogenates limits the interpretation of these studies, the [3H]haloperidol binding site and adenylate cyclase sensitivity of dopamine were studied in the isolated proximal convoluted tubule and pars recta of the rabbit kidney. [3H]Haloperidol binding sites were saturable, stereoselective and of high affinity. The apparent dissociation constant was 31.5 .times. 10-9 M (.+-. 8.5) and the maximum receptor density was 0.31 .times. 10-15 M (.+-. 0.08)/mm. In pars recta specific binding was 53% of total [3H]haloperidol binding. Dopamine stimulated adenylate cyclase activity in a dose-related manner, which was inhibited by cis-flupenthixol but not by trans-flupenthixol or (-)-propranolol. The stimulatory effect of the dopamine 1 (D1) agonist SKF 82526 on adenylate cyclase activity was blocked by the D1 antagonist SCH 23390. Dopamine receptors in the proximal convoluted tubule appear to be of the D1 subtype since they are linked to stimulation of adenylate cyclase. This is further substantiated by the stereoselectivity for (+)-sulpiride (a D1 antagonist), which had a greater affinity for the [3H]haloperidol binding site than (-)-sulpiride (a D2 antagonist).