Stimulation of (Ca2+ + Mg2+)-ATPase activity in human erythrocyte membranes by synthetic lysophosphatidic acids and lysophosphatidylcholines. Effects of chain length and degree of unsaturation of the fatty acid groups.
Synthetic lysophosphatidic acids and lysophosphatidylcholines were examined for their effects on the (Ca2+ + Mg2+)-ATPase of human erythrocyte membranes. Addition of these compounds to erythrocyte ghosts caused significant changes in ATPase activity. The degree of unsaturation and the length of the sn-1 long chain hydrocarbon moiety were both contributing factors. All lysophosphatidic acids tested stimulated (Ca2+ + Mg2+)-ATPase activity. Of the species having a saturated acyl group, the most active was the myristoyl derivative. Linoleoyllysophosphatidic acid was the most potent of the unsaturated species. Saturated lysophosphatidylcholines with a short chain fatty acyl group (C10 to C14) exhibited only a moderate stimulatory activity, whereas the longer chain homologues, i.e., C16 and C18 were inhibitory at high concentrations. On the other hand, unsaturated lysophosphatidylcholines had stimulatory activities comparable to the unsaturated lysophosphatidic acids. These results suggest that the acidic moiety of lysophosphatidic acid is not an important structural determinant for expressing ATPase stimulatory activity in ghosts. Rather the nature of the hydrocarbon chain as well as the lyso structure of these compounds appear most critical under these conditions. The stimulatory effects of lysophosphatidic acids or lysophosphatidylcholines were additive to that induced with calmodulin, suggesting that these lysophospholipids affect the (Ca2+ + Mg2+)-ATPase by a mechanism which is different from that seen with calmodulin.
Tokumura
A
A
Mostafa
M H
MH
Nelson
D R
DR
Hanahan
D J
DJ
D000328:Adult; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases / Q000097:blood*; D002147:Calmodulin / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008246:Lysophospholipids; D010712:Phosphatidic Acids / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D002147:Calmodulin; D005231:Fatty Acids, Unsaturated; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D010712:Phosphatidic Acids; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases