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J Biol Chem, Vol. 273, Issue 24, 15192-15202, June 12, 1998

Co-expression of a Ca2+-inhibitable Adenylyl Cyclase and of a Ca2+-sensing Receptor in the Cortical Thick Ascending Limb Cell of the Rat Kidney
INHIBITION OF HORMONE-DEPENDENT cAMP ACCUMULATION BY EXTRACELLULAR Ca2+

Marie Céleste de Jesus Ferreira, Cécile Héliès-Toussaint, Martine Imbert-Teboul, Claire Bailly, Jean-Marc Verbavatz, Anne-Christine Bellanger, and Danielle Chabardès

From the Service de Biologie Cellulaire, Département de Biologie Cellulaire et Moléculaire, CEA Saclay, France

The Ca2+-sensing receptor protein and the Ca2+-inhibitable type 6 adenylyl cyclase mRNA are present in a defined segment of the rat renal tubule leading to the hypothesis of their possible functional co-expression in a same cell and thus to a possible inhibition of cAMP content by extracellular Ca2+. By using microdissected segments, we compared the properties of regulation of extracellular Ca2+-mediated activation of Ca2+ receptor to those elicited by prostaglandin E2 and angiotensin II. The three agents inhibited a common pool of hormone-stimulated cAMP content by different mechanisms as follows. (i) Extracellular Ca2+, coupled to phospholipase C activation via a pertussis toxin-insensitive G protein, induced a dose-dependent inhibition of cAMP content (1.25 mM Ca2+ eliciting 50% inhibition) resulting from both stimulation of cAMP hydrolysis and inhibition of cAMP synthesis; this latter effect was mediated by capacitive Ca2+ influx as well as release of intracellular Ca2+. (ii) Angiotensin II, coupled to the same transduction pathway, also decreased cAMP content; however, its inhibitory effect on cAMP was mainly accounted for by an increase of cAMP hydrolysis, although angiotensin II and extracellular Ca2+ can induce comparable release of intracellular Ca2+. (iii) Prostaglandin E2, coupled to pertussis toxin-sensitive G protein, inhibited the same pool of adenylyl cyclase units as extracellular Ca2+ but by a different mechanism. The functional properties of the adenylyl cyclase were similar to those described for type 6. The results establish that the co-expression of a Ca2+-inhibitable adenylyl cyclase and of a Ca2+-sensing receptor in a same cell allows an inhibition of cAMP accumulation by physiological concentrations of extracellular Ca2+.


Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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