Actions of cadmium on basolateral plasma membrane proteins involved in calcium uptake by fish intestine.
The inhibition of Ca(2+)-ATPase, (Na+ + K+)-ATPase and Na+/Ca2+ exchange by Cd2+ was studied in fish intestinal basolateral plasma membrane preparations. ATP driven 45Ca2+ uptake into inside-out membrane vesicles displayed a Km for Ca2+ of 88 +/- 17 nM, and was extremely sensitive to Cd2+ with an IC50 of 8.2 +/- 3.0 pM Cd2+, indicating an inhibition via the Ca2+ site. (Na+ + K+)-ATPase activity was half-maximally inhibited by micromolar amounts of Cd2+, displaying an IC50 of 2.6 +/- 0.6 microM Cd2+. Cd2+ ions apparently compete for the Mg2+ site of the (Na+ + K+)-ATPase. The Na+/Ca2+ exchanger was inhibited by Cd2+ with an IC50 of 73 +/- 11 nM. Cd2+ is a competitive inhibitor of the exchanger via an interaction with the Ca2+ site (Ki = 11 nM). Bepridil, a Na+ site specific inhibitor of Na+/Ca2+ exchange, induced an additional inhibition, but did not change the Ki of Cd2+. Also, Cd2+ is exchanged against Ca2+, albeit to a lesser extent than Ca2+. The exchanger is only partly blocked by the binding of Cd2+. In vivo cadmium that has entered the enterocyte may be shuttled across the basolateral plasma membrane by the Na+/Ca2+ exchanger. We conclude that intracellular Cd2+ ions will inhibit plasma membrane proteins predominantly via a specific interaction with divalent metal ion sites.
Schoenmakers
T J
TJ
Department of Animal Physiology, Faculty of Science, University of Nijmegen, The Netherlands.
Klaren
P H
PH
Flik
G
G
Lock
R A
RA
Pang
P K
PK
Bonga
S E
SE
D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D010471:Perches; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D015220:Calcium Channels; D008565:Membrane Proteins; D015222:Sodium Channels; D002104:Cadmium; D012964:Sodium; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium