Calcium-dependent regulation of phospholipid methylation in rabbit platelets.
Effects of Ca2+ on phospholipid methylation in rabbit platelet membranes were studied using S-adenosyl-L-[3H-methyl]methionine as a substrate. The methylation was inhibited to 30% of the basal activity with 100 microM Ca2+. The inhibition was completely counteracted by various calmodulin antagonists. Their concentrations, i.e., N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, chlorpromazine and trifluoperazine, to be required for half maximal recovery were 32, 47 and 29 microM, respectively. In contrast, N-(6-aminohexyl)-1-naphthalenesulfonamide, a weaker calmodulin antagonist, did not lead to a sufficient recovery of the inhibition. Addition of exogenous phosphatidyl-N-monomethylethanolamine (PMME) and phosphatidyl-N,N-dimethylethanolamine, intermediates of phosphatidylcholine synthesis by successive methylation of phosphatidylethanolamine (PE), enhanced the formation of 3H-methylated products. However, the increased amount of 3H-methylated products by the addition of those intermediates was much the same either in the presence or absence of Ca2+. These results suggest that the Ca2+-induced inhibition of methylation in platelets is mediated either by calmodulin itself or by a site which has calmodulin antagonist binding properties similar to this protein and that Ca2+ seems to inhibit the first step of the methylation to form PMME from PE.
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000494:pharmacology; D002148:Calmodulin-Binding Proteins; D002462:Cell Membrane / Q000378:metabolism; D002798:Diacylglycerol Cholinephosphotransferase / Q000378:metabolism; D008745:Methylation; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000494:pharmacology; D011817:Rabbits
D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D002798:Diacylglycerol Cholinephosphotransferase; D010749:Phosphoprotein Phosphatases; D002118:Calcium