Guillon G, Gallo-Payet N, Balestre M N, Lombard C
Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
Biochem J. 1988 Aug 1;253(3):765-75. doi: 10.1042/bj2530765.
Vasopressin (VP) and angiotensin II (AT II) stimulate the production of inositol phosphates (IP) in rat glomerulosa cells. Guanosine 5'-[gamma-thio]triphosphate (GTP[S]), but not VP or AT II, stimulates IP production in a myo-[3H]inositol-prelabelled glomerulosa-cell membrane preparation. In combination with GTP[S], these hormones potentiate the response to GTP[S], indicating the existence of a G-protein involved in the coupling of the VP and AT II receptor with the phospholipase C. ADP-ribosylation with pertussis toxin (IAP) revealed the specific labelling of a single molecule of 41 kDa. No significant inhibition of VP- or AT II-stimulated IP accumulation was detected in intact cells when the whole 41 kDa molecule was endogenously ADP-ribosylated by IAP treatment. On the contrary, when glomerulosa cells were infected with cholera toxin (CT), both the VP- and AT II-stimulated IP accumulations were inhibited in a dose-dependent manner. Yet these effects were partial even at high concentrations of CT, and could not be related to the ADP-ribosylation of 'alpha s' molecules. Similarly, when the cells were infected with 1 microgram of CT/ml, the specific binding of VP and AT II decreased by 50-60%. Such results may signify that the treatment primarily affects the densities of the hormone receptors. When glomerulosa cells were incubated for 15 h in the presence of 10 nM-corticotropin (ACTH), a condition in which the intracellular concentration of cyclic AMP was increased 3-fold, the maximum IP response to 0.1 microM-VP or -AT II was decreased by 50%. When similar experiments were carried out only after a 15 min incubation period with the same concentration of ACTH, the increase in cyclic AMP was more pronounced, but no inhibition of hormone-induced IP accumulation was observed. Altogether, these results may suggest that CT exerts its action on the VP- or AT II-sensitive phospholipase C systems via a prolonged increase in intracellular cyclic AMP.
血管加压素（VP）和血管紧张素II（AT II）可刺激大鼠肾小球膜细胞中肌醇磷酸（IP）的产生。鸟苷5'-[γ-硫代]三磷酸（GTP[S]）而非VP或AT II可刺激预先用肌醇-[3H]标记的肾小球膜细胞膜制剂中IP的产生。与GTP[S]联合使用时，这些激素可增强对GTP[S]的反应，表明存在一种参与VP和AT II受体与磷脂酶C偶联的G蛋白。百日咳毒素（IAP）进行的ADP核糖基化显示出对一个41 kDa单分子的特异性标记。当整个41 kDa分子通过IAP处理在内源上进行ADP核糖基化时，在完整细胞中未检测到对VP或AT II刺激的IP积累有明显抑制作用。相反，当肾小球膜细胞感染霍乱毒素（CT）时，VP和AT II刺激的IP积累均以剂量依赖性方式受到抑制。然而，即使在高浓度的CT下，这些作用也是部分性的，并且与“αs”分子的ADP核糖基化无关。同样，当细胞以1μg CT/ml感染时，VP和AT II的特异性结合减少了50-60%。这些结果可能表明该处理主要影响激素受体的密度。当肾小球膜细胞在10 nM促肾上腺皮质激素（ACTH）存在下孵育15小时时，在此条件下细胞内环磷酸腺苷（cAMP）的细胞内浓度增加了3倍，对0.1μM VP或-AT II的最大IP反应降低了50%。当仅在相同浓度的ACTH孵育15分钟后进行类似实验时，cAMP的增加更为明显，但未观察到对激素诱导的IP积累的抑制作用。总之，这些结果可能表明CT通过细胞内环磷酸腺苷的长期增加对VP或AT II敏感的磷脂酶C系统发挥作用。
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