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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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Copyright © 1998 by the American Society for Biochemistry and Molecular Biology.
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