Ambient C1- ions modify rat mesangial cell contraction by modulating cell inositol trisphosphate and Ca2+ via enhanced prostaglandin E2

Abstract

Our recent observation showed that angiotensin II (AII) and arginine vasopressin (AVP) stimulate Ca2+-activated Cl- conductance in mesangial cells. These data raise the possibility that mesangial cell function may be modulated by extracellular chloride concentration [( Cl-]o). The present study was undertaken to test this possibility using cultured rat mesangial cells. When the [Cl-]o was reduced to zero, the percentage of mesangial cells showing contraction responding to AII and AVP was decreased from 72 +/- 9 to 33 +/- 10% and from 60 +/- 4 to 24 +/- 11%, respectively. Ca2+ transients induced by AII and AVP, measured in mesangial cells loaded with Ca2+-sensitive photoprotein aequorin, were attenuated as [Cl-]o decreased. Also, when [Cl-]o decreased, inositol trisphosphate (IP3) levels of mesangial cells were suppressed, both in the presence and absence of AII or AVP. PGE2 production by mesangial cells increased when [Cl-]o decreased and the effects of ambient Cl- deprivation could be restored by addition of indomethacin to the Cl- -free medium. Moreover, PGE2 decreased mesangial cell contractility, Ca2+ transients, and IP3 production in response to AII and AVP. These data suggest that the decrease in [Cl-]o attenuates mesangial cell contraction by suppressing IP3 production and thus Ca2+ transients in response to AII and AVP through enhanced PGE2 production.