Putney J W, Aub D L, Taylor C W, Merritt J E
Fed Proc. 1986 Oct;45(11):2634-8.
A wide variety of receptors appear to be coupled to a phospholipase C (EC 3.1.4.3) that hydrolyzes inositol lipids. This reaction is believed to provide a link between receptor activation and cellular Ca2+ mobilization. The mechanisms by which this occurs are believed to involve inositol 1,4,5-trisphosphate (1,4,5-IP3), which signals release of Ca2+ from the endoplasmic reticulum. In rat parotid acinar cells made permeable with saponin, 1,4,5-IP3 induced rapid release of sequestered Ca2+. In intact parotid cells, the concentration-response relationship for methacholine-induced IP3 formation was similar to the relationship for muscarinic receptor occupancy by methacholine. About 10-fold lower concentrations of methacholine were sufficient to increase cytosolic [Ca2+] and to activate secretion, indicating an excess IP3 forming capacity for the muscarinic receptor. The mechanisms for the coupling of receptors to IP3 formation were studied in pancreatic acinar cells made permeable electrically. In this preparation, nonhydrolyzable derivatives of GTP potentiated agonist-induced IP3 production, which suggests the involvement of a guanine nucleotide-dependent regulatory protein. The effects of agonists and guanine nucleotides were not altered by pretreating the acinar cells with cholera or pertussis toxins, which indicated that the regulatory protein linking receptors to IP3 formation is distinct from the ones involved in the regulation of adenylate cyclase.
多种受体似乎都与能水解肌醇脂质的磷脂酶C（EC 3.1.4.3）偶联。据信该反应在受体激活与细胞内钙离子动员之间建立了联系。其发生机制据信涉及肌醇1,4,5 -三磷酸（1,4,5 - IP3），它能促使内质网释放钙离子。在用皂角苷处理使其具有通透性的大鼠腮腺腺泡细胞中，1,4,5 - IP3能诱导被隔离的钙离子快速释放。在完整的腮腺细胞中，乙酰甲胆碱诱导IP3形成的浓度 - 反应关系与乙酰甲胆碱占据毒蕈碱受体的关系相似。浓度约低10倍的乙酰甲胆碱就足以增加胞质钙离子浓度并激活分泌，这表明毒蕈碱受体形成IP3的能力过剩。在用电使其具有通透性的胰腺腺泡细胞中研究了受体与IP3形成的偶联机制。在这种制备条件下，鸟苷三磷酸的不可水解衍生物增强了激动剂诱导的IP3生成，这表明涉及一种依赖鸟嘌呤核苷酸的调节蛋白。用霍乱毒素或百日咳毒素预处理腺泡细胞，并不改变激动剂和鸟嘌呤核苷酸的作用，这表明将受体与IP3形成联系起来的调节蛋白与参与腺苷酸环化酶调节的蛋白不同。
