A putative lectin-binding receptor mediates cadmium-evoked calcium release.
Nanomolar concentrations of cadmium (Cd2+) produce an immediate rise in free Ca2+ in human dermal fibroblasts, which is mostly caused by the release of stored Ca2+ via inositol trisphosphate. Here we have used lectins to evaluate the hypothesis that a cell surface glycoprotein mediates the response to Cd2+. A prior incubation with wheat germ agglutinin (WGA) or certain other lectins inhibited calcium release evoked by Cd2+. WGA reversibly inhibited Cd(2+)-evoked calcium release as indicated by measurements of cytosolic free Ca2+ and 45Ca2+ efflux. WGA half-maximally inhibited Ca2+ release at 1.2 x 10(-7) M. The Kd for the binding of fluoresceinylated WGA was 2.8 x 10(-7) M. Chitotriose dissociated fluoresceinylated WGA from the cells and restored cadmium responsiveness. WGA inhibited Cd(2+)-evoked 45Ca2+ efflux similarly at 18 and 37 degrees C. A brief incubation with chitotriose at 18 or 10 degrees C reversed the inhibition by WGA. WGA neither bound 109Cd2+ nor affected 109Cd2+ uptake by the cells. Succinylated WGA, which binds N-acetylglucosamine but not N-acetylneuraminic acid, failed to inhibit Ca2+ release evoked by Cd2+. WGA probably inhibits Ca2+ release produced by Cd2+ by binding to N-acetylneuraminic acid in the external domain of a plasma membrane receptor.
Chen
Y C
YC
Department of Pharmacology, School of Medicine, University of Alabama, Birmingham 35294.
Smith
J B
JB
D000372:Agglutination Tests; D002104:Cadmium / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D037102:Lectins / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000187:drug effects / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism*; D014312:Trisaccharides; D014909:Wheat Germ Agglutinins / Q000378:metabolism
D037102:Lectins; D008562:Membrane Glycoproteins; D011975:Receptors, Mitogen; D012795:Sialoglycoproteins; D014312:Trisaccharides; D014909:Wheat Germ Agglutinins; D002104:Cadmium; C041161:chitotriose; D002118:Calcium