Howard S, Chan-Yeung M, Martin L, Phaneuf S, Salari H
Department of Medicine, University of British Columbia, Vancouver, Canada.
Eur J Pharmacol. 1992 Oct 1;227(2):123-9. doi: 10.1016/0922-4106(92)90119-g.
Leukotriene D4 (LTD4) at concentrations greater than 1 nM induced phosphatidylinositol bisphosphate (PIP2) hydrolysis and protein kinase C (PKC) activation in primary culture of airway smooth muscle cells. Within seconds of activation, an increase in inositol 1,4,5-trisphosphate (IP3) was observed reaching a maximum at 5 min. The level of IP3 decreased after 5 min and was followed by an increase in inositol 1,4-bisphosphate (IP2) and inositol 1-monophosphate (IP1). LTD4-induced PIP2 hydrolysis was inhibited by 1 h pretreatment of cells with 10 micrograms/ml of pertussis toxin (PTX). LTD4 activated both soluble and particulate forms of PKC by 2-3-fold. The LTD4-induced PKC activation was blocked by treatment of cells with PTX, suggesting the involvement of a PTX-sensitive G-protein. To assess the involvement of G(i) in smooth muscle cell receptor activation, the modulation of adenylyl cyclase activity was investigated. LTD4 did not stimulate cAMP formation in smooth muscle cells, and did not inhibit forskolin-induced cAMP formation. These data suggest that the LTD4 receptor in airway smooth muscle cells is coupled to a PTX-sensitive G-protein, possibly G(o).
浓度大于1 nM的白三烯D4（LTD4）可诱导气道平滑肌细胞原代培养物中的磷脂酰肌醇二磷酸（PIP2）水解和蛋白激酶C（PKC）激活。激活后数秒内，观察到肌醇1,4,5-三磷酸（IP3）增加，在5分钟时达到最大值。5分钟后IP3水平下降，随后肌醇1,4-二磷酸（IP2）和肌醇一磷酸（IP1）增加。用10微克/毫升百日咳毒素（PTX）预处理细胞1小时可抑制LTD4诱导的PIP2水解。LTD4使可溶性和颗粒性形式的PKC均激活2-3倍。用PTX处理细胞可阻断LTD4诱导的PKC激活，提示存在对PTX敏感的G蛋白参与其中。为评估G(i)在平滑肌细胞受体激活中的作用，研究了腺苷酸环化酶活性的调节。LTD4未刺激平滑肌细胞中的cAMP形成，也未抑制福斯可林诱导的cAMP形成。这些数据表明，气道平滑肌细胞中的LTD4受体与对PTX敏感的G蛋白偶联，可能是G(o)。
