The role of calcium ions in the process of acetyltransferase activation during the formation of platelet-activating factor (PAF-acether)

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Abstract
The role of Ca2+ in the activation of the enzyme lyso-(platelet-activating factor):acetyl-CoA [coenzyme A] acetyltransferase was studied in rat peritoneal macrophages in response to complement-coated zymosan particles and ionophore A23187. By using Ca2+-containing buffers, a threshold concentration of extracellular Ca2+ > 1 .mu.M was found to be necessary to observe the activation of the enzyme in response to zymosan. By contrast, a significant role of intracellular Ca2+ in this process could be ruled out, since the putative intracellular Ca-transport antagonist TMB-8 [8-(NN-diethylamino)octyl-3,4,5-trimethoxybenzoate] did not inhibit the activation of the acetyltransferase induced by zymosan in the presence of extracellular Ca2+. The link between acetyltransferase activation and extracellular Ca2+ transport was studied by measuring Ca2+ uptake in response to the stimuli. Zymosan particles induced a rapid increment in cell-associated Ca2+ which correlated well with the extent of acetyltransferase activation (r = 0.91) and with the release of platelet-activating factor (r = 0.95) in response to different doses of zymosan. Cellular Ca2+ efflux in response to zymosan particles was also measured and found to be increased, as compared with controls, when the activation of the acetyltransferase declined. The entry of extracellular Ca2+ into the cell apparently is a crucial event in the activation of acetyltransferase and, thereby, in the formation of platelet-activating factor in rat peritoneal macrophages.

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