Andersen H, Bjerregaard H, Nielsen R
Institute of Biological Chemistry A, University of Copenhagen, Denmark.
Acta Physiol Scand. 1990 Oct;140(2):199-208. doi: 10.1111/j.1748-1716.1990.tb08992.x.
In the present study we have examined the action of the phorbol diester tetradecanoyl phorbol acetate, an activator of protein kinase C, on the transepithelial transport of sodium, chloride and water and the production of cAMP in the isolated frog skin epithelium (Rana esculenta). Addition of tetradecanoyl phorbol acetate to the mucosal solution resulted initially in an increase in the short-circuit current, which was followed by a progressive decrease. If the short-circuit current was first activated by addition of the antidiuretic hormone, arginine vasotocin, then the addition of tetradecanoyl phorbol acetate resulted only in a pronounced inhibition. The changes in the short-circuit current were the result of changes in the active influx of Na+. The effect of tetradecanoyl phorbol acetate on the intracellular potential measured under short-circuited conditions (Vscc) was time-dependent. Just after addition of tetradecanoyl phorbol acetate to the mucosal solution, Vscc depolarized; this was followed by a slight hyperpolarization, after which Vscc continued to decline. The inhibition of the Na+ transport by tetradecanoyl phorbol acetate was associated with a decline in the response to the antidiuretic hormone (arginine vasotocin), but the ability of arginine vasotocin to increase the cellular level of cAMP and to stimulate the osmotic water flow was not affected by the presence of tetradecanoyl phorbol acetate. In skin halves in which the short-circuit current was stimulated with arginine vasotocin, addition of tetradecanoyl phorbol acetate resulted in a dose-dependent inhibition of the short-circuit current, but only minor changes in Vscc were observed. The results presented suggest that the addition of tetradecanoyl phorbol acetate to the isolated frog skin first increases and then decreases the arginine vasotocin-sensitive sodium permeability of the apical membrane. This might be due to a stimulating effect of tetradecanoyl phorbol acetate on both the activation and deactivation (turnover) of the sodium channels.
在本研究中，我们检测了佛波酯十四酰佛波醇乙酸酯（一种蛋白激酶C激活剂）对离体青蛙皮肤上皮组织（食用蛙）中钠、氯和水的跨上皮转运以及环磷酸腺苷（cAMP）产生的作用。将十四酰佛波醇乙酸酯添加到黏膜溶液中，最初会导致短路电流增加，随后逐渐降低。如果短路电流首先通过添加抗利尿激素精氨酸血管加压素被激活，那么再添加十四酰佛波醇乙酸酯只会导致明显的抑制作用。短路电流的变化是Na⁺主动内流变化的结果。十四酰佛波醇乙酸酯对在短路条件下测量的细胞内电位（Vscc）的影响是时间依赖性的。在将十四酰佛波醇乙酸酯添加到黏膜溶液后，Vscc立即去极化；随后出现轻微的超极化，之后Vscc继续下降。十四酰佛波醇乙酸酯对Na⁺转运的抑制与对抗利尿激素（精氨酸血管加压素）反应的下降有关，但精氨酸血管加压素增加细胞内cAMP水平和刺激渗透水流的能力不受十四酰佛波醇乙酸酯存在的影响。在用精氨酸血管加压素刺激短路电流的皮肤半叶中，添加十四酰佛波醇乙酸酯会导致短路电流呈剂量依赖性抑制，但仅观察到Vscc有微小变化。所呈现的结果表明，向离体青蛙皮肤添加十四酰佛波醇乙酸酯首先会增加然后降低顶端膜对精氨酸血管加压素敏感的钠通透性。这可能是由于十四酰佛波醇乙酸酯对钠通道的激活和失活（周转）均有刺激作用。
