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This Article Full Text Full Text (PDF) All Versions of this Article: 286/6/F1120    most recent 00433.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Pedrosa, R. Articles by Soares-da-Silva, P. Search for Related Content PubMed PubMed Citation Articles by Pedrosa, R. Articles by Soares-da-Silva, P.

Defective D₁-like receptor-mediated inhibition of the Cl^–/HCO₃^– exchanger in immortalized SHR proximal tubular epithelial cells

¹Institute of Pharmacology and Therapeutics Faculty of Medicine, 4200 Porto, Portugal; and ²Department of Pediatrics, Georgetown University, 20007 Washington, District of Columbia

Submitted 9 December 2003 ; accepted in final form 9 February 2004

The sensitivity of the Cl^–/HCO₃^– exchanger to dopamine D₁- and D₂-like receptor stimulation in immortalized renal proximal tubular epithelial cells from the spontaneous hypertensive rat (SHR) and Wistar-Kyoto rat (WKY) was examined. The activity of the Cl^–/HCO₃^– exchanger (in pH U/s) in SHR cells (0.00191) was greater than in WKY cells (0.00126). The activity of Cl^–/HCO₃^– exchanger was exclusively observed at the apical cell side and probably occurs through the SLC26A6 anion transporter that is expressed in both WKY and SHR cells. Stimulation of D₁-like receptors with SKF-38393 markedly attenuated the HCO₃^–-dependent intracellular pH recovery in WKY cells but not in SHR cells. Stimulation of D₂-like receptors with quinerolane did not alter Cl^–/HCO₃^– exchanger activity in both WKY and SHR cells. The selective D₁-like receptor antagonist SKF-83566 prevented the effect of SKF-38393. Both WKY and SHR cells responded to dibutyryl-cAMP (DBcAMP) with inhibition of the Cl^–/HCO₃^– exchanger, and downregulation of PKA (overnight exposure to DBcAMP) abolished the inhibitory effect of both DBcAMP and SKF-38393 in WKY cells. Both SHR and WKY cells responded to forskolin with increases in the formation of cAMP. However, only WKY responded to SKF-38393 with increases in the formation of cAMP that was prevented by SKF-83566. It is concluded that WKY cells respond to D₁-like dopamine receptor stimulation with inhibition of the apical Cl^–/HCO₃^– (SLC26A6) exchanger and SHR cells have a defective D₁-like dopamine response.

SLC26A6; hypertension; spontaneous hypertensive rat; Wistar-Kyoto rat

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