Dopamine receptor subtypes in renal brush border and basolateral membranes

Abstract

Dopamine (DA) modulates renal tubular sodium transport by actions at both brush border (BBM) and basolateral membranes (BLM). DA receptors have been demonstrated in proximal tubule but the subtype of DA receptor in either BBM or BLM has not been determined. DA-1 receptors were quantitated by the specific binding of 125I-SCH 23982, a DA-1 antagonist (defined by 20 μM SCH 23390, a DA-1 antagonist) and DA-2 receptors by the specific binding of 3H-methyl-spiroperidol or 3H-spiroperidol (defined by 30 μM trifluperidol, a predominantly DA-2 antagonist). The specific binding of 125I-SCH 23982 and 3H-methyl-spiroperidol or 3H-spiroperidol were saturable with time and ligand concentration and reversible. Analysis of Rosenthal plots by non-linear regression revealed a high affinity site and a very low affinity site for both BLM and BBM. Maximum receptor density was similar in BBM and BLM. Competition experiments with 125I-SCH 23982 revealed high and low affinity binding sites in both BBM and BLM. The high affinity site was characteristic of a DA-1 receptor. Competition experiments with 3H-spiroperidol were also suggestive of DA-2 receptors. DA-1 but not DA-2 drugs increased adenylate cyclase and phospholipase-C activities in both BBM and BLM. However, their effects were greater in BLM than BBM. We conclude that DA-1 and DA-2 receptors are present in both BBM and BLM in canine kidney. Renal DA-1 receptors are linked to stimulation of both adenylate cyclase and phospholipase-C activity.