Inhibition of Na,K-ATPase and sodium pump by anticancer ether lipids and protein kinase C inhibitors ET-18-OCH3 and BM 41.440.
The anticancer ether lipid analogs ET-18-OCH3 and BM 41.440 inhibited Na, K-ATPase in the purified rat brain membrane fragments, with a potency comparable to that of their inhibition of protein kinase C. They also inhibited Na,K-ATPase in the crude membrane fraction of HL60 cells. Kinetic analysis indicated that the lipids had a mode of action different from that of ouabain, a classic inhibitor of the ATPase. The lipids also blocked 22Na uptake in the inside-out membrane vesicles of human erythrocytes. It is suggested that Na,K-ATPase might represent an additional site with which certain protein kinase C inhibitors can interact to alter cellular activities.
Oishi
K
K
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322.
Zheng
B
B
White
J F
JF
Vogler
W R
WR
Kuo
J F
JF
D000818:Animals; D000970:Antineoplastic Agents; D002462:Cell Membrane / Q000201:enzymology; D002540:Cerebral Cortex / Q000201:enzymology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000201:enzymology; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010742:Phospholipid Ethers / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects*; D012979:Sodium Radioisotopes / Q000097:blood; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013574:Synaptosomes / Q000201:enzymology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008244:Lysophosphatidylcholines; D010742:Phospholipid Ethers; D015222:Sodium Channels; D012979:Sodium Radioisotopes; C026659:edelfosine; D010042:Ouabain; C043297:ilmofosine; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase