Extracellular Ca2+ decreases chloride reabsorption in rat CTAL by inhibiting cAMP pathway.
The effect of activation of the Ca2+-sensing receptor on net Cl flux (JCl) has been investigated on microperfused cortical (C) thick ascending limb (TAL) from rat kidney. Increasing bath Ca2+ from 0.5 to 3 mM or adding 200 microM of the specific Ca2+-sensing receptor agonist neomycin reduced basal as well as antidiuretic hormone (ADH)-stimulated JCl by 27.7 +/- 5.0% and 25.9 +/- 4.1%, respectively. JCl remained unchanged in time control tubules. The effect of neomycin/Ca2+ on JCl 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 JCl and prevented a further effect of 3 mM Ca2+. When JCl was increased by 8-bromo-cAMP plus IBMX, no effect of 3 mM Ca2+ was observed. Inhibitors of phospholipase A2 and cytochrome P-450 monooxygenase failed to modify the effect of 3 mM Ca2+, although these agents dampened significantly the inhibitory effect of bradykinin on medullary TAL. We conclude that extracellular Ca2+ decreases basal and ADH-stimulated Cl reabsorption in CTAL by inhibiting the cAMP pathway, independently of protein kinase C or phospholipase A2 stimulation.
Unité de Recherche Associée Centre National de la Recherche Scientifique 1859, Département de Biologie Cellulaire et Moléculaire, Commissariat à l'Energie Atomique-Saclay, 91191 Gif-sur-Yvette, France.
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De Jesus Ferreira
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Bailly
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000502:physiology*; D007679:Kidney Medulla / Q000502:physiology; D007684:Kidney Tubules / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D009355:Neomycin / Q000494:pharmacology; D010477:Perfusion; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides; D014667:Vasopressins / Q000494:pharmacology
D002712:Chlorides; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007211:Indoles; D007546:Isoquinolines; D008301:Maleimides; D013449:Sulfonamides; D014667:Vasopressins; D015124:8-Bromo Cyclic Adenosine Monophosphate; C044388:N-(2-aminoethyl)-5-isoquinolinesulfonamide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D009355:Neomycin; C070515:bisindolylmaleimide I; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D001920:Bradykinin; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine