The carcinogen Cd2+ activates InsP(3)-mediated Ca2+ release through a specific metal ions receptor in Xenopus oocyte

The effects of the carcinogen Cd2+ on Xenopus oocyte were evaluated by Inos itol (1,4,5)-trisphosphate (InsP(3)) assays and electrophysiological experi ments. The stimulation of the Ca2+-dependent Cl- current by Cd2+ is clearly linked to InsP(3) formation since the effects of the metal are antagonized by neomycin, heparin and caffeine. A similar inhibition of the Cd2+ effect s is observed when the oocytes are pretreated with thapsigargin. Moreover, the use of sulfhydryl groups reductors such as 2-mercaptoethanol or N-ethyl maleimide strongly suggests that the Cd2+ response is mediated by an extrac ellular receptor. Finally, measurements of InsP(3) production demonstrate t hat Cd2+ superfusion actually leads to a PIP2 breakdown. We conclude that e xtracellular Cd2+ evokes an increase in [Ca2+](i) by stimulating the emptyi ng of the InsP(3)-sensitive Ca2+ stores, and that it may do so by interacti ng with a specific cell-surface ion receptor. This putative ion receptor ma y be important in allowing oocytes to respond to heavy metals. (C) 2000 Els evier Science Inc. All rights reserved.