DOPAMINE INHIBITS AVP-DEPENDENT NA-4-LIKE RECEPTOR( TRANSPORT AND WATER PERMEABILITY IN RAT CCD VIA A D)

We studied the receptor responsible for dopamine action in isolated pe rfused cortical collecting ducts (CCD) from rats treated with deoxycor ticosterone. (Critical experiments were repeated in CCD from untreated rats with the same results.) At doses greater than or equal to 1 mu M , dopamine inhibited arginine vasopressin (AVP)-dependent Na+ and wate r transport (measured by the unidirectional lumen-to-bath Na-22(+) flu x and the transepithelial voltage) end osmotic water permeability (P-f ). The effects of dopamine were not reversed by the dopamine-1 (D-1) a ntagonist SCH-23390, and no inhibition was produced by the D-1 agonist s fenoldopam or SKF-81247. When Na+ transport and P-f were stimulated with 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate plus 3 -isobutyl-1-methylxanthine, dopamine did not inhibit, suggesting a ''D -2-type'' receptor. However, the D-2 agonist quinpirole had no effect on the AVP-dependent transepithelial voltage (V-T), and the D-2 and D- 3 antagonists domperidone and pimozide did not reverse dopamine inhibi tion of V-T. The only agent tested that reversed the effects of dopami ne was the D-4-specific antagonist clozapine. We conclude that dopamin e inhibition of salt and water transport in the CCD is mediated by a D -4-like receptor.