The role of phosphatidylinosides-Ca^<2+> system in asthma attack

为探讨磷脂酰肌醇-Ca ^<2+>系统在支气管哮喘发作中的作用，本研究从生理、生化和药理学方面进行了探讨。在这项研究中，使用猪气管平滑肌，它被发现，佛波酯激活蛋白激酶C，诱发大量增加的钙内流，即使在小的膜去极化的收缩激动剂，通过受体激活的功能。已知收缩激动剂通过受体激活刺激气道平滑肌细胞中的肌醇磷脂代谢，导致产生三磷酸肌醇和二酰基甘油，其激活蛋白激酶C。因此，可以得出结论，在存在三种激动剂的情况下，对较低浓度组胺的反应（PGF、氨甲酰胆碱和5-羟色胺）主要依赖于外源性钙内流，激动剂引起的蛋白激酶C激活和膜去极化可能是组胺引起的钙内流增加，最终增强组胺收缩的原因。结果表明，PACAP的两种形式均可通过提高组织cAMP水平而发挥新型的气管平滑肌松弛剂的作用，PMN膜结合型磷脂酶A2的活性似乎受GTP结合蛋白的直接调节，因此，我们应进一步阐明三磷酸肌醇-Ca ^2+系统在支气管哮喘中的作用。

To elucidate the functions of phosphatidylinosides-Ca^<2+> system in asthma attack in patients with bronchial asthma, and physiological, biochemical and pharmacological approaches were performed in this study. In this study using swine tracheal smooth muscle, it was found that phorbol ester which activated protein kinase C, evoked large increases of Ca influx even at small membrane depolarization by contractile agonists that function through receptor activations. It is known that contractile agonists through receptor activations stimulate inositol phospholipid metabolisms in airway smooth muscle cells, resulting in the production of inositol trisphosphate and diacylglycerol which activates protein kinase C. Thus, it is concluded that the responses to slower concentrations of histamine in the presence of the three agonists (PGF, carbachol and serotonin) is mainly dependent on the influx of external Ca and that the agonists-induced activaton of protein kinase C as well as membrane depolarization may be responsible for the increase of the histamine-induced Ca influx, eventually enhancing the histamine contractions.In addition, we showed that both forms of PACAP tested may act as novel potent relaxants on tracheal smooth muscle by raising tissue cyclic AMP levels and membrane-binding phospholipase A2 activity of PMN would thus appea to be regulated directly by GTP-binding protein.We should try on next steps to elucidate the functions of inositol triphosphate-Ca^<2+> system in bronchial asthma.