Heyworth C M, Wilson S P, Gawler D J, Houslay M D
FEBS Lett. 1985 Aug 5;187(2):196-200. doi: 10.1016/0014-5793(85)81241-2.
The phorbol ester TPA (12-O-tetradecanoyl phorbol-13-acetate) causes a dose-dependent inhibition of the glucagon-stimulated adenylate cyclase activity expressed in plasma membranes isolated from TPA-treated hepatocytes. However, no observable inhibitory effect of TPA on adenylate cyclase activity was observed in cells which had been exposed to glucagon for 5 min, prior to isolation, to desensitise adenylate cyclase. The degree of inhibition of adenylate cyclase elicited by both glucagon desensitisation and TPA treatment of hepatocytes was identical. Pre-treatment of hepatocytes with TPA was also found to prevent glucagon from blocking insulin's activation of the peripheral plasma membrane cyclic AMP phosphodiesterase in intact hepatocytes. TPA treatment also inhibited the ability of cholera toxin to activate the peripheral cyclic AMP phosphodiesterase in intact hepatocytes. It is suggested that in these particular instances TPA and glucagon elicit mutually exclusive processes rather than TPA mimicking glucagon desensitisation per se.
佛波酯TPA(12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯)对从经TPA处理的肝细胞分离的质膜中表达的胰高血糖素刺激的腺苷酸环化酶活性产生剂量依赖性抑制。然而,在分离前已暴露于胰高血糖素5分钟以使腺苷酸环化酶脱敏的细胞中,未观察到TPA对腺苷酸环化酶活性有明显的抑制作用。胰高血糖素脱敏和TPA处理肝细胞所引起的腺苷酸环化酶抑制程度是相同的。还发现用TPA预处理肝细胞可防止胰高血糖素阻断完整肝细胞中胰岛素对外周质膜环磷酸腺苷磷酸二酯酶的激活。TPA处理也抑制了霍乱毒素激活完整肝细胞中外周环磷酸腺苷磷酸二酯酶的能力。有人提出,在这些特定情况下,TPA和胰高血糖素引发相互排斥的过程,而不是TPA本身模拟胰高血糖素脱敏。