Actions of cadmium on basolateral plasma membrane proteins involved in calcium uptake by fish intestine

• Published in: The Journal of membrane biology 1992-05, Vol.127 (3), p.161-172
• Main Authors: SCHOENMAKERS, T. J. M, KLAREN, P. H. M, FLIK, G, LOCK, R. A. C, PANG, P. K. T, WENDELAAR BONGA, S. E
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; biological membranes; cadmium; Cadmium - pharmacology; calcium; Calcium - metabolism; Calcium Channels - metabolism; Calcium-Transporting ATPases - metabolism; Cell physiology; effects on; fish physiology; Freshwater; Fundamental and applied biological sciences. Psychology; inhibition; Intestinal Mucosa - enzymology; Intestinal Mucosa - metabolism; intestine; intestines; Male; Membrane and intracellular transports; Membrane Proteins - drug effects; Membrane Proteins - metabolism; Molecular and cellular biology; Na super(+)/K super(+)-transporting ATPase; Oreochromis mossambicus; Perches; Sodium - metabolism; Sodium Channels - metabolism; Sodium-Potassium-Exchanging ATPase - metabolism; uptake
• ISSN: 0022-2631; 1432-1424
• DOI: 10.1007/BF00231504

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.