title: D2-like receptor-mediated inhibition of Na+-K+-ATPase activity is dependent on the opening of K+ channels.
abstract: 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+ (I(K)) currents in opossum kidney cells were measured. The inhibitory effect of dopamin 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 microM), but not apamin (1 microM), 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 I(K) 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 I(K). Both H-89 (protein kinase A inhibitor) and chelerythrine (protein kinase C inhibitor) failed to prevent the stimulatory effect of quinerolane on I(K). 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.
authors.affiliation: Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200 Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Gomes
authors.forename: P
authors.initials: P
authors.lastname: Soares-Da-Silva
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002460:Cell Line; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015640:Ion Channel Gating / Q000502:physiology; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D009893:Opossums; D037342:Pertussis Toxin; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012964:Sodium / Q000493:pharmacokinetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000666:Amphotericin B; D000935:Antifungal Agents; D002316:Cardiotonic Agents; D004298:Dopamine; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D005905:Glyburide; D007004:Hypoglycemic Agents; D037342:Pertussis Toxin; D020110:Pinacidil; D015221:Potassium Channels; D011804:Quinolines; D017448:Receptors, Dopamine D2; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D013469:Sulpiride; D014665:Vasodilator Agents; D010566:Virulence Factors, Bordetella; C113776:dopamine D2L receptor; C044846:SKF83566; C047726:quinelorane