Abdel-Latif A A, Zhang Y W
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
Invest Ophthalmol Vis Sci. 1991 Jul;32(8):2432-8.
The authors investigated the effects of endothelin-1 (ET1) on inositol trisphosphate (IP3) production, 1, 2-diacylglycerol (DAG) formation, measured as phosphatidic acid (PA), cAMP formation, and contraction in iris sphincter of different mammalian species. They found that ET1 is a potent agonist for IP3 production, DAG formation, and contraction in rabbit, dog, cat, and pig iris sphincters, and for cAMP formation in all species that were investigated--rabbit, dog, cat, pig, bovine, monkey, and human sphincters. In the bovine model, ET1 induced cAMP formation in a dose-dependent manner, with an EC50 of 28 nM. This is the first report that showed an effect of the peptide on the adenylate cyclase system. In rabbit sphincter, ET1 induced a significant increase in IP3 production by 30 sec and reached a 6-fold level more than control within 1 and 5 min. ET1-stimulated IP3 production is dose dependent with an EC50 of 45 nM, this value is about 100- and 56-fold lower than those we reported for substance P and carbachol, respectively. ET1 also increased 32P labeling of PA more than 6-fold; and in rabbit sphincter, ET1 is a more potent agonist in contracting the sphincter than in contracting the dilator (the EC50 values for sphincter and dilator were 46 and 120 nM, respectively). L-type Ca2+ channels are not involved in IP3- and contraction responses because several blockers of these channels did not affect the ET1-induced responses, implying that in the iris sphincter, ET1 elicits the physiologic response through the G protein activation of phospholipase C and/or adenylate cyclase and not through the activation of voltage-dependent Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
作者研究了内皮素-1（ET1）对不同哺乳动物物种虹膜括约肌中肌醇三磷酸（IP3）生成、以磷脂酸（PA）衡量的1,2-二酰甘油（DAG）形成、环磷酸腺苷（cAMP）生成以及收缩的影响。他们发现，ET1是兔、犬、猫和猪虹膜括约肌中IP3生成、DAG形成及收缩的强效激动剂，在所有被研究物种（兔、犬、猫、猪、牛、猴和人括约肌）中均能促进cAMP生成。在牛模型中，ET1以剂量依赖方式诱导cAMP生成，半数有效浓度（EC50）为28 nM。这是首份显示该肽对腺苷酸环化酶系统有作用的报告。在兔括约肌中，ET1在30秒时使IP3生成显著增加，并在1分钟和5分钟内达到比对照高6倍的水平。ET1刺激的IP3生成具有剂量依赖性，EC50为45 nM，该值分别比我们报道的P物质和卡巴胆碱低约100倍和56倍。ET1还使PA的32P标记增加超过6倍；在兔括约肌中，ET1在收缩括约肌方面比收缩瞳孔开大肌更有效（括约肌和瞳孔开大肌的EC50值分别为46和120 nM）。L型钙通道不参与IP3和收缩反应，因为这些通道的几种阻滞剂不影响ET1诱导的反应，这意味着在虹膜括约肌中，ET1通过G蛋白激活磷脂酶C和/或腺苷酸环化酶引发生理反应，而非通过激活电压依赖性钙通道。（摘要截短于25
