Schnefel S, Banfic H, Eckhardt L, Schultz G, Schulz I
Max-Planck-Institut für Biophysik, Frankfurt, Main, FRG.
FEBS Lett. 1988 Mar 28;230(1-2):125-30. doi: 10.1016/0014-5793(88)80655-0.
We have studied the involvement of GTP-binding proteins in the stimulation of phospholipase C from rat pancreatic acinar cells. Pretreatment of permeabilized cells with activated cholera toxin inhibited both cholecystokinin-octapeptide (CCK-OP) and GTP gamma S but not carbachol (CCh)-induced production of inositol trisphosphate. Pertussis toxin had no effect. Neither vasoactive intestinal polypeptide, a stimulator of adenylyl cyclase, nor the cAMP-analogue, 8-bromo cAMP, mimicked the inhibitory effect of cholera toxin on agonist-induced phospholipase C activation. This indicates that inhibition by cholera toxin could not be attributed to a direct interaction of cholera toxin activated Gs with phospholipase C or to an elevation of cAMP. In isolated rat pancreatic plasma membranes cholera toxin ADP-ribosylated a 40 kDa protein, which was inhibited by CCK-OP but not by CCh. We conclude from these data that both CCK- and muscarinic acetylcholine receptors functionally couple to phospholipase C by two different GTP-binding proteins.
我们研究了GTP结合蛋白在刺激大鼠胰腺腺泡细胞磷脂酶C中的作用。用活化的霍乱毒素预处理通透细胞，可抑制胆囊收缩素八肽（CCK-OP）和GTPγS诱导的肌醇三磷酸生成，但不抑制卡巴胆碱（CCh）诱导的生成。百日咳毒素无作用。血管活性肠肽（一种腺苷酸环化酶刺激剂）和cAMP类似物8-溴cAMP均不能模拟霍乱毒素对激动剂诱导的磷脂酶C激活的抑制作用。这表明霍乱毒素的抑制作用不能归因于霍乱毒素激活的Gs与磷脂酶C的直接相互作用，也不能归因于cAMP的升高。在分离的大鼠胰腺质膜中，霍乱毒素使一种40 kDa的蛋白质发生ADP核糖基化，该蛋白质受CCK-OP抑制，但不受CCh抑制。从这些数据我们得出结论，CCK受体和毒蕈碱型乙酰胆碱受体通过两种不同的GTP结合蛋白在功能上与磷脂酶C偶联。
