Effects of extracellular sodium on cytosolic calcium, PGE2 and cAMP in papillary collecting tubule cells.
An increase in cytosolic calcium (Cai2+), induced by an increase in extracellular calcium concentration or addition of the calcium ionophore A23187, has been shown to suppress basal and AVP responsive cAMP and inhibit water flow in the collecting tubule. In the present study, the relationships between extracellular Na+ concentration, Cai2+, PGE2 and AVP-responsive cAMP production were examined in cultured rat papillary collecting tubule (RPCT) cells. Reducing extracellular Na+ concentration from 144 to 24 mM increased Cai2+ and PGE2 production approximately below 144 mM on Cai2+ or PGE2 was not due to a change in media osmolality or chloride concentration, since these parameters were maintained at constant levels by addition of tetramethylammonium chloride (TMA) or choline chloride. Exposure of RPCT cells to media containing 24 mM Na+ significantly suppressed basal and AVP responsive cAMP compared to that observed at 144 mM Na+. This suppression was mimicked by the calcium ionophore A23187 which also increased Cai2+ and PGE2. The increase in Cai2+ and PGE2 and the suppression of basal and AVP responsive cAMP, which were observed at 24 versus 144 mM Na+, were abolished in calcium free media and were likely due to influx of extracellular calcium. Indomethacin did not prevent the suppressive effects of reducing extracellular Na+ concentration below 144 mM on basal or AVP responsive cAMP, suggesting that the enhanced production of PGE2 did not mediate the reduction in AVP responsiveness. In contrast to cAMP, reductions in extracellular Na+ concentration from 144 to 24 mM did not influence basal cGMP or the cGMP responses to atrial natriuretic peptide or nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)
Craven
P A
PA
Department of Medicine, University of Pittsburgh, Pennsylvania.
DeRubertis
F R
FR
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D007474:Ion Exchange; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology*
D001127:Arginine Vasopressin; D012964:Sodium; D000242:Cyclic AMP; D006152:Cyclic GMP; D015232:Dinoprostone; D002118:Calcium