A study of cadmium transport pathways using the Caco-2 cell model.
The purpose of this study was to investigate the mechanism by which cadmium (Cd2+) crosses the intestinal epithelium using a Caco-2 cell model. Experimentation was designed to determine which of several possible pathways of transport are operative. These pathways include passive diffusion, transport via a calcium pathway, sulfhydryl-mediated transport, and carrier-mediated (active transport and/or facilitated diffusion) transport. To examine the diffusion pathway the effect of various apical cadmium concentrations on the amount of cadmium transported was tested. The effects of verapamil, calcium, and 1,25(OH)2 vitamin D3 (vit. D3) on Cd2+ transport were examined to investigate the possible existence of a calcium transport pathway. N-Ethylmaleimide, a sulfhydryl group blocker, was used to determine whether Cd2+ transport is sulfhydryl-mediated. Active transport was evaluated by examining the effect of 2,4-dinitrophenol, a metabolic inhibitor, on the transport of Cd2+. These studies indicated that: (1) a portion of the overall transport of Cd2+ can be attributed to diffusion, (2) stimulation of calcium binding protein transcription by vit. D3 enhances Cd2+ transport, and (3) the transport process for Cd2+ has both sulfhydryl-mediated and carrier-mediated components.
Pigman
E A
EA
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721, USA.
Blanchard
J
J
Laird
H E
HE
D019297:2,4-Dinitrophenol / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D018938:Caco-2 Cells / Q000378:metabolism*; D002104:Cadmium / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002762:Cholecalciferol / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002104:Cadmium; D002762:Cholecalciferol; D014700:Verapamil; D005033:Ethylmaleimide; D019297:2,4-Dinitrophenol; D002118:Calcium