Evidence suggesting that a novel guanine nucleotide regulatory protein couples receptors to phospholipase C in exocrine pancreas.
Evidence suggesting that a novel guanine nucleotide regulatory protein couples receptors to phospholipase C in exocrine pancreas.
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有证据表明，一种新型鸟嘌呤核苷酸调节蛋白将受体与外分泌胰腺中的磷脂酶 C 偶联。
DOI：
10.1042/bj2360337
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
PutneyJr,JW
中科院分区：
文献类型：
--
作者：
Merritt,JE;Taylor,CW;Rubin,RP;PutneyJr,JW
许多细胞对“Ca2+动员”激动剂的最初反应是磷脂酶 C 介导的磷脂酰肌醇二磷酸水解为肌醇三磷酸 (IP3) 和二酰基甘油。通过与腺苷酸环化酶的受体调节类比，有人提出“Ca2+动员”受体可能与鸟嘌呤核苷酸结合蛋白（G蛋白）相互作用来调节磷脂酶C活性。在这里，我们报告了电透化的大鼠胰腺腺泡细胞中对雨蛙素或卡巴胆碱的反应，IP3 的积累增加。 GTP 的稳定类似物（鸟苷 5'-[γ-硫代]三磷酸和鸟苷 5'-[β, γ-亚氨基]三磷酸）可刺激 IP3 积累并增强雨蛙素和卡巴胆碱的作用。这种协同作用证明了受体、G 蛋白和磷脂酶 C 之间的相互作用。在产生 Gi 和 Gs（将受体与腺苷酸环化酶偶联的蛋白质）大量共价修饰的条件下，用百日咳或霍乱毒素预处理细胞，不会影响这些反应。因此，我们得出结论，外分泌胰腺中将受体与磷脂酶 C 偶联的 G 蛋白可能既不是 Gi 也不是 Gs；相反，我们认为是一种不同的 G 蛋白介导了这种效应。
The initial response of many cells to ‘Ca2+-mobilizing’ agonists is phospholipase C-mediated hydrolysis of phosphatidylinositol bisphosphate to inositol trisphosphate (IP3) and diacylglycerol. It has been suggested, by analogy with receptor regulation of adenylate cyclase, that ‘Ca2+-mobilizing’ receptors may interact with a guanine nucleotide-binding protein (G protein) to regulate phospholipase C activity. Here we report increased accumulation of IP3 in response to caerulein or carbachol in electrically permeabilized rat pancreatic acinar cells. The stable analogues of GTP (guanosine 5′-[gamma–thio]trisphosphate and guanosine 5′-[beta, gamma-imido]triphosphate) stimulate IP3 accumulation and potentiate the effects of caerulein and carbachol. This synergism demonstrates an interaction between receptors, a G protein and phospholipase C. These responses are unaffected by pretreatment of the cells with pertussis or cholera toxins under conditions that produce substantial covalent modification of Gi and Gs, the proteins that couple receptors to adenylate cyclase. We therefore conclude that the G protein that couples receptors to phospholipase C in exocrine pancreas is probably neither Gi nor Gs; instead, we propose that a different G protein mediates this effect.