Burch R M
Nova Pharmaceutical Corporation, Baltimore, Maryland 21224.
J Cardiovasc Pharmacol. 1990;15 Suppl 6:S44-5.
Kinins elicit prostaglandin and inositol phosphate production in 3T3 fibroblasts through stimulation of B2 receptors. Prostaglandin synthesis is maximum by 5 min, whereas inositol phosphate production continues for longer than 30 min. Prostaglandin synthesis is stimulated by phospholipase A2, which releases arachidonate from phospholipids, whereas a phosphatidylinositol-specific phospholipase C catalyzes formation of equimolar amounts of inositol phosphate and diacylglycerol. Stimulation of these two second-messenger systems occurs through independent pathways: (a) dexamethasone inhibits prostaglandin formation by inhibiting phospholipase A2, and, to a lesser degree, cyclooxygenase, but is without effect on inositol phosphate production; (b) neomycin inhibits inositol phosphate production without affecting prostaglandin synthesis; (c) phorbol esters inhibit inositol phosphate production while augmenting prostaglandin synthesis; and (d) indomethacin inhibits prostaglandin synthesis but does not affect inositol phosphate production. At later times (greater than 10 min), the two pathways interact. Stimulation with one agonist to increase diacylglycerol results in augmentation of prostaglandin synthesis in response to a second agonist. Inositol phosphates cause release of calcium from intracellular stores. Prostaglandins stimulate (by binding to their own receptors) adenylate cyclase to increase cAMP. Additionally, prostaglandins increase intracellular free calcium by increasing influx of extracellular calcium. Both inositol phosphates and prostaglandins play roles in mitogenesis in these cells.
激肽通过刺激B2受体引发3T3成纤维细胞中前列腺素和肌醇磷酸的产生。前列腺素合成在5分钟时达到最大值，而肌醇磷酸的产生持续超过30分钟。前列腺素合成由磷脂酶A2刺激，该酶从磷脂中释放花生四烯酸，而磷脂酰肌醇特异性磷脂酶C催化等摩尔量的肌醇磷酸和二酰甘油的形成。这两个第二信使系统的刺激通过独立途径发生：（a）地塞米松通过抑制磷脂酶A2并在较小程度上抑制环氧化酶来抑制前列腺素的形成，但对肌醇磷酸的产生没有影响；（b）新霉素抑制肌醇磷酸的产生而不影响前列腺素的合成；（c）佛波酯抑制肌醇磷酸的产生，同时增强前列腺素的合成；（d）吲哚美辛抑制前列腺素的合成，但不影响肌醇磷酸的产生。在后期（大于10分钟），这两个途径相互作用。用一种激动剂刺激以增加二酰甘油会导致对第二种激动剂的反应中前列腺素合成增加。肌醇磷酸导致细胞内储存释放钙。前列腺素（通过与自身受体结合）刺激腺苷酸环化酶以增加cAMP。此外，前列腺素通过增加细胞外钙的流入来增加细胞内游离钙。肌醇磷酸和前列腺素在这些细胞的有丝分裂中都起作用。
