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  • Title: Defective D1-like receptor-mediated inhibition of the Cl-/HCO3- exchanger in immortalized SHR proximal tubular epithelial cells.
    Author: Pedrosa R, Jose PA, Soares-da-Silva P.
    Journal: Am J Physiol Renal Physiol; 2004 Jun; 286(6):F1120-6. PubMed ID: 14970001.
    Abstract:
    The sensitivity of the Cl(-)/HCO(3)(-) exchanger to dopamine D(1)- and D(2)-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(-)/HCO(3)(-) exchanger (in pH U/s) in SHR cells (0.00191) was greater than in WKY cells (0.00126). The activity of Cl(-)/HCO(3)(-) 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 D(1)-like receptors with SKF-38393 markedly attenuated the HCO(3)(-)-dependent intracellular pH recovery in WKY cells but not in SHR cells. Stimulation of D(2)-like receptors with quinerolane did not alter Cl(-)/HCO(3)(-) exchanger activity in both WKY and SHR cells. The selective D(1)-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(-)/HCO(3)(-) 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 D(1)-like dopamine receptor stimulation with inhibition of the apical Cl(-)/HCO(3)(-) (SLC26A6) exchanger and SHR cells have a defective D(1)-like dopamine response.
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