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1 Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Porto, Portugal
2 Department of Pediatrics, Georgetown University, Washington, DC, USA
* To whom correspondence should be addressed. E-mail: psoaresdasilva{at}netcabo.pt.
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 units/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 pHi recovery in WKY cells, but not in SHR cells. Stimulation of D2-like receptors with quinerolane did not alter Cl-/HCOM3- 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 cylic AMP (db-cAMP) with inhibition of the Cl-/HCO3- exchanger and downregulation of protein kinase A (PKA, overnight exposure to db-cAMP) abolished the inhibitory effect of both db-cAMP and SKF38393 in WKY cells. Both SHR and WKY cells responded to forskolin with increases in the formation of cyclic AMP. However, only WKY responded to SKF 38393 with increases in the formation of cyclic AMP 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.
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