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Abstract The effect of activation of the Ca 2+ -sensing receptor on net Cl flux ( J Cl ) has been investigated on microperfused cortical (C) thick ascending limb (TAL) from rat kidney. Increasing bath Ca 2+ from 0.5 to 3 mM or adding 200 μM of the specific Ca 2+ -sensing receptor agonist neomycin reduced basal as well as antidiuretic hormone (ADH)-stimulated J Cl by 27.7 ± 5.0% and 25.9 ± 4.1%, respectively. J Cl remained unchanged in time control tubules. The effect of neomycin/Ca 2+ on J Cl was blocked by two protein kinase A inhibitors, H-9 or H-89, but not by a protein kinase C inhibitor, GF-109203X, regardless of whether ADH was present or not. Moreover, H-89 decreased basal J Cl and prevented a further effect of 3 mM Ca 2+ . When J Cl was increased by 8-bromo-cAMP plus IBMX, no effect of 3 mM Ca 2+ was observed. Inhibitors of phospholipase A 2 and cytochrome P -450 monooxygenase failed to modify the effect of 3 mM Ca 2+ , although these agents dampened significantly the inhibitory effect of bradykinin on medullary TAL. We conclude that extracellular Ca 2+ decreases basal and ADH-stimulated Cl reabsorption in CTAL by inhibiting the cAMP pathway, independently of protein kinase C or phospholipase A 2 stimulation. calcium in vitro microperfusion protein kinases Footnotes Address for reprint requests: C. Bailly, URA 1859, SBCe/DBCM, Bât. 520, CEA-Saclay, 91191 Gif-sur-Yvette, France. This work was supported by a predoctoral fellowship from the Ministère de l’Education Nationale, de la Recherche et de la Technologie. Copyright © 1998 the American Physiological Society
AJP - Renal Physiology – The American Physiological Society
Published: Aug 1, 1998
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