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Am J Physiol Renal Physiol 283: F114-F123, 2002. First published January 29, 2002; doi:10.1152/ajprenal.00244.2001
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Vol. 283, Issue 1, F114-F123, July 2002

D2-like receptor-mediated inhibition of Na+-K+-ATPase activity is dependent on the opening of K+ channels

Pedro Gomes and P. Soares-da-Silva

Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200 Porto, Portugal

This study examined the effects of D2-like dopamine receptor activation on Na+-K+-ATPase activity while apical-to-basal, ouabain-sensitive, amphotericin B-induced increases in short-circuit current and basolateral K+ (IK) currents in opossum kidney cells were measured. The inhibitory effect of dopamine on Na+-K+-ATPase activity was completely abolished by either D1- or D2-like receptor antagonists and mimicked by D1- and D2-like receptor agonists SKF-38393 and quinerolane, respectively. Blockade of basolateral K+ channels with BaCl2 (1 mM) or glibenclamide (10 µM), but not apamin (1 µM), totally prevented the inhibitory effects of quinerolane. The K+ channel opener pinacidil decreased Na+-K+-ATPase activity. The inhibitory effect of quinerolane on Na+-K+- ATPase activity was abolished by pretreatment of opossum kidney cells with pertussis toxin (PTX). Quinerolane increased IK across the basolateral membrane in a concentration-dependent manner; this effect was abolished by pretreatment with PTX, S-sulpiride, and glibenclamide. SKF-38393 did not change IK. Both H-89 (protein kinase A inhibitor) and chelerythrine (protein kinase C inhibitor) failed to prevent the stimulatory effect of quinerolane on IK. The stimulation of the D2-like receptor was associated with a rapid hyperpolarizing effect, whereas D1-like receptor activation was accompanied by increases in cell membrane potential. It is concluded that stimulation of D2-like receptors leads to inhibition of Na+-K+-ATPase activity and hyperpolarization; both effects are associated with the opening of K+ channels.

potassium channels; dopamine type 2-like receptors; cyclic adenosine 5'-monophosphate; opossum kidney cells


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