Dieter P, Schulze-Specking A, Decker K
Biochemisches Institut, Universität Freiburg im Breisgau, Federal Republic of Germany.
Eur J Biochem. 1988 Oct 15;177(1):61-7. doi: 10.1111/j.1432-1033.1988.tb14345.x.
The release of the prostanoids prostaglandin D2 (PGD2), prostaglandin E2 (PGE2) and thromboxane induced by zymosan and phorbol ester in cultured rat Kupffer cells was found to depend on the extracellular concentration of Ca2+ to some extent. Prostanoid formation following the addition of the calcium ionophore A 23187 was totally inhibited when calcium ions were withdrawn from the medium whereas the prostanoid synthesis from added arachidonic acid was independent of Ca2+. A half-maximal rate of PGE2 release by cells treated with zymosan, phorbol ester or A23187 was obtained at 0.6-0.7 microM free extracellular Ca2+ and greater than or equal to 100 microM free Ca2+ was required to stimulate PGE2 formation maximally. The calmodulin antagonist R24571 partially inhibited the release of PGE2 elicited by zymosan and A23187 but not by phorbol ester or arachidonic acid. Verapamil and nifedipine, two calcium channel blockers, had no effect on the formation of PGE2 irrespective of the stimulus. TMB 8 [3,4,5-trimethoxybenzoic acid 8-(diethylamino)-octyl ester] an intracellular calcium antagonist, inhibited the synthesis of PGE2 induced by zymosan and phorbol ester. The superoxide formation following the addition of zymosan and phorbol ester was not influenced by removal of calcium ions from the medium or by addition of the various calcium antagonists. The data presented here suggest that Ca2+-dependent reactions are involved in the synthesis of prostanoids induced by zymosan and phorbol ester and that both extracellular Ca2+ and mobilization of Ca2+ from intracellular stores are needed to induce maximally the production of prostanoids in cultured rat Kupffer cells.
已发现酵母聚糖和佛波酯在培养的大鼠库普弗细胞中诱导的前列腺素D2（PGD2）、前列腺素E2（PGE2）和血栓素的释放，在一定程度上取决于细胞外Ca2+的浓度。当从培养基中去除钙离子时，添加钙离子载体A 23187后前列腺素的形成被完全抑制，而从添加的花生四烯酸合成前列腺素则与Ca2+无关。用酵母聚糖、佛波酯或A23187处理的细胞，在细胞外游离Ca2+浓度为0.6 - 0.7微摩尔时获得PGE2释放的半数最大速率，最大程度刺激PGE2形成需要大于或等于100微摩尔的游离Ca2+。钙调蛋白拮抗剂R24571部分抑制酵母聚糖和A23187引发的PGE2释放，但不抑制佛波酯或花生四烯酸引发的释放。两种钙通道阻滞剂维拉帕米和硝苯地平，无论刺激因素如何，对PGE2的形成均无影响。细胞内钙拮抗剂TMB 8 [3,4,5 - 三甲氧基苯甲酸8 - （二乙氨基） - 辛酯]抑制酵母聚糖和佛波酯诱导的PGE2合成。添加酵母聚糖和佛波酯后超氧化物的形成不受从培养基中去除钙离子或添加各种钙拮抗剂的影响。此处呈现的数据表明，Ca2+依赖性反应参与酵母聚糖和佛波酯诱导的前列腺素合成，并且细胞外Ca2+和从细胞内储存库中动员Ca2+对于在培养的大鼠库普弗细胞中最大程度诱导前列腺素的产生都是必需的。
