The carcinogen Cd(2+) activates InsP(3)-mediated Ca(2+) release through a specific metal ion receptor in Xenopus oocyte.
The effects of the carcinogen Cd(2+) on Xenopus oocyte were evaluated by Inositol (1,4,5)-trisphosphate (InsP(3)) assays and electrophysiological experiments. The stimulation of the Ca(2+)-dependent Cl(-) current by Cd(2+) 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 Cd(2+) effects is observed when the oocytes are pretreated with thapsigargin. Moreover, the use of sulfhydryl groups reductors such as 2-mercaptoethanol or N-ethylmaleimide strongly suggests that the Cd(2+) response is mediated by an extracellular receptor. Finally, measurements of InsP(3) production demonstrate that Cd(2+) superfusion actually leads to a PIP(2) breakdown. We conclude that extracellular Cd(2+) evokes an increase in [Ca(2+)](i) by stimulating the emptying of the InsP(3)-sensitive Ca(2+) stores, and that it may do so by interacting with a specific cell-surface ion receptor. This putative ion receptor may be important in allowing oocytes to respond to heavy metals.
Hague
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F
Université de Picardie Jules Verne, Faculté des Sciences, Laboratoire de Neurobiologie Cellulaire, 33 rue Saint Leu, 80039 Amiens cedex 1, France.
Matifat
F
F
Louvet
L
L
Brûle
G
G
Collin
T
T
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D002352:Carrier Proteins / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D017136:Ion Transport / Q000187:drug effects; D008246:Lysophospholipids / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects*; D008623:Mercaptoethanol / Q000494:pharmacology; D008845:Microinjections; D009355:Neomycin / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism; D014982:Xenopus laevis
D000873:Anthracenes; D002352:Carrier Proteins; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D008565:Membrane Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; C076381:cadmium receptor; D002104:Cadmium; D002110:Caffeine; D004533:Egtazic Acid; D008623:Mercaptoethanol; D019284:Thapsigargin; C010030:9-anthroic acid; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D009355:Neomycin; D005033:Ethylmaleimide