Coupling of endothelin B receptors to the calcium pump and phospholipase C via Gs and Gq in rat liver.
Coupling of endothelin B receptors to the calcium pump and phospholipase C via Gs and Gq in rat liver.
复制标题
大鼠肝脏中内皮素 B 受体通过 Gs 和 Gq 与钙泵和磷脂酶 C 偶联。
DOI：
10.1016/s0021-9258(17)42104-1
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
S. Lotersztajn
中科院分区：
文献类型：
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作者：
C. Jouneaux;A. Mallat;C. Serradeil‐Le Gal;P. Goldsmith;J. Hanoune;S. Lotersztajn
我们已经证明，在雄性大鼠的肝脏中，内皮素A（ETA）和ETB受体以相等的比例共存，ETA受体介导了糖原分解的钙依赖性激活。我们在这里描述的性别差异内皮素作用在肝细胞中，因为在雌性大鼠中，80%的ET受体是ETB型，因此，激活糖原分解是ETB介导的过程（EC 50 = 0.03 pM）。ET-1刺激雌性大鼠的糖原分解是连续激活磷脂酰肌醇4，5-二磷酸水解（EC 50 = 0.03 pM）和抑制质膜中的钙挤出泵（IC 50 = 0.03 pM），ET-1近似于sarafotoxin S6 C近似于ET-3。GTP γ S可增强内皮素对各效应子的调节。ET-1不刺激腺苷酸环化酶活性。为了鉴定将ETB受体偶联至每个效应物的鸟嘌呤核苷酸调节蛋白（G蛋白）的性质，我们使用了针对不同G蛋白α亚基的COOH末端的抗体。与Gs α（RM）反应的抗体阻断了ET-1对钙泵的抑制作用，但不影响ET-1对磷脂酶C的刺激作用。与Gq α（QL）反应的抗体剂量依赖性地拮抗ET-1和加压素对磷脂酶C的刺激，而不影响ET-1对钙泵的抑制。与Gi 1 α/Gi 2 α（AS）反应的抗体对两个系统均无影响。我们的结论是，在肝细胞内皮素引起的钙信号不仅是连续的磷脂酶C的激活，但也抑制质膜钙泵，每个效应器耦合到ETB受体的不同G蛋白，Gq，和Gs。
We have demonstrated in liver from male rats that both endothelin A (ETA) and ETB receptors coexist in equal proportion and that ETA receptors mediate a calcium-dependent activation of glycogenolysis. We describe here a sex difference in endothelin action in hepatocytes because, in female rats, 80% of the ET receptors are of ETB type and, accordingly, activation of glycogenolysis is an ETB-mediated process (EC50 = 0.03 pM). ET-1 stimulation of glycogenolysis in female rats was consecutive to activation of phosphatidylinositol 4,5-bisphosphate hydrolysis (EC50 = 0.03 pM) and to inhibition of the calcium extrusion pump (IC50 = 0.03 pM) in plasma membranes, with ET-1 approximately sarafotoxin S6C approximately ET-3. Endothelin regulation of each effector was potentiated by GTP gamma S. ET-1 did not stimulate adenylyl cyclase activity. To identify the nature of the guanine nucleotide regulatory proteins (G protein(s)) coupling ETB receptors to each effector, we used antibodies against the COOH terminus of different G protein alpha subunits. Antibodies reactive with Gs alpha (RM) blocked ET-1 inhibition of the calcium pump, while they did not affect ET-1 stimulation of phospholipase C. Antibodies reactive with Gq alpha (QL) dose-dependently antagonized stimulation of phospholipase C by ET-1 and vasopressin, without affecting ET-1 inhibition of the calcium pump. Antibodies reactive with Gi1 alpha/Gi2 alpha (AS) had no effect on either system. We conclude that the calcium signal provoked by endothelins in hepatocyte is not only consecutive to activation of phospholipase C but also to inhibition of the plasma membrane calcium pump, each effector being coupled to ETB receptors by different G proteins, Gq, and Gs.