Calcium-sensing receptor attenuates AVP-induced aquaporin-2 expression via a calmodulin-dependent mechanism.
Recent evidence suggests that arginine vasopressin (AVP)-dependent aquaporin-2 expression is modulated by the extracellular calcium-sensing receptor (CaSR) in principal cells of the collecting duct, but the signaling pathways mediating this effect are unknown. Using a mouse cortical collecting duct cell line (mpkCCD(cl4)), we found that increasing the concentration of apical extracellular calcium or treating with the CaSR agonists neomycin or Gd(3+) attenuated AVP-dependent accumulation of aquaporin-2 mRNA and protein; CaSR gene-silencing prevented this effect. Calcium reduced the AVP-induced accumulation of cAMP, but this did not occur by increased degradation of cAMP by phosphodiesterases or by direct inhibition of adenylate cyclase. Notably, the effect of extracellular calcium on AVP-dependent aquaporin-2 expression was prevented by inhibition of calmodulin. In summary, our results show that high concentrations of extracellular calcium attenuate AVP-induced aquaporin-2 expression by activating the CaSR and reducing coupling efficiency between V(2) receptor and adenylate cyclase via a calmodulin-dependent mechanism in cultured cortical collecting duct cells.
Bustamante
Mauro
M
Service of Nephrology, Fondation pour Recherches Médicales, 64 Ave de la Roseraie, CH-1211 Genève 4, Switzerland.
Hasler
Udo
U
Leroy
Valérie
V
de Seigneux
Sophie
S
Dimitrov
Mitko
M
Mordasini
David
D
Rousselot
Martine
M
Martin
Pierre-Yves
PY
Féraille
Eric
E
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D051399:Aquaporin 2 / Q000235:genetics*; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology* / Q000502:physiology; D002147:Calmodulin / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D016133:Polymerase Chain Reaction; D044169:Receptors, Calcium-Sensing / Q000187:drug effects / Q000502:physiology*; D017483:Receptors, Vasopressin / Q000502:physiology
D051399:Aquaporin 2; D002147:Calmodulin; D044169:Receptors, Calcium-Sensing; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000262:Adenylyl Cyclases; D002118:Calcium