title: Calcium-sensing receptor attenuates AVP-induced aquaporin-2 expression via a calmodulin-dependent mechanism.
abstract: 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.
authors.affiliation: Service of Nephrology, Fondation pour Recherches Médicales, 64 Ave de la Roseraie, CH-1211 Genève 4, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Bustamante
authors.forename: Udo
authors.initials: U
authors.lastname: Hasler
authors.forename: Valérie
authors.initials: V
authors.lastname: Leroy
authors.forename: Sophie
authors.initials: S
authors.lastname: de Seigneux
authors.forename: Mitko
authors.initials: M
authors.lastname: Dimitrov
authors.forename: David
authors.initials: D
authors.lastname: Mordasini
authors.forename: Martine
authors.initials: M
authors.lastname: Rousselot
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Martin
authors.forename: Eric
authors.initials: E
authors.lastname: Féraille
mesh_terms: 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
chemical_list: D051399:Aquaporin 2; D002147:Calmodulin; D044169:Receptors, Calcium-Sensing; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000262:Adenylyl Cyclases; D002118:Calcium