Wright C D, Hoffman M D, Thueson D O, Conroy M C
Pharmacology Department, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Biochem Biophys Res Commun. 1987 Nov 13;148(3):1110-7. doi: 10.1016/s0006-291x(87)80247-4.
3,7-Dimethoxy-4-phenyl-N-1H tetrazol-5-yl-4H-furo[3,2-b]-indole-2- carboxamide, L-arginate (CI-922) is a potent inhibitory of human neutrophil functions in response to a variety of stimuli. In this report, the effects of CI-922 on specific processes involved in stimulus-response coupling are evaluated. CI-922 does not inhibit human neutrophil phospholipase C or protein kinase C activities. CI-922 is shown to inhibit calmodulin-dependent enzyme activation. The calmodulin antagonist activity is confirmed by calmodulin-Sepharose affinity chromatography. These results suggest that CI-922 inhibits neutrophil activation by preventing the activation of calmodulin-dependent enzymes, implying a critical role for such enzymes in stimulus-response coupling.
3,7-二甲氧基-4-苯基-N-1H四唑-5-基-4H-呋喃并[3,2-b]吲哚-2-甲酰胺L-精氨酸盐（CI-922）是一种对多种刺激产生反应的人类中性粒细胞功能的强效抑制剂。在本报告中，评估了CI-922对刺激-反应偶联中涉及的特定过程的影响。CI-922不抑制人类中性粒细胞磷脂酶C或蛋白激酶C的活性。已表明CI-922可抑制钙调蛋白依赖性酶的激活。钙调蛋白拮抗剂活性通过钙调蛋白-琼脂糖亲和色谱法得到证实。这些结果表明，CI-922通过阻止钙调蛋白依赖性酶的激活来抑制中性粒细胞的激活，这意味着此类酶在刺激-反应偶联中起关键作用。
