ATP和UTP与分离的肝细胞的复杂相互作用。有多少种受体？

The complex interaction of ATP and UTP with isolated hepatocytes. How many receptors?

Keppens S

Department of Biochemistry, Faculty of Medicine, Katholieke Universiteit te Leuven, Belgium.

Gen Pharmacol. 1993 Mar;24(2):283-9. doi: 10.1016/0306-3623(93)90304-g.

Abstract

ATP exerts multiple receptor-mediated effects on isolated hepatocytes: glycogenolysis through the activation of glycogen phosphorylase (cAMP-independent, IP3/calcium-mediated), inactivation of glycogen synthase, inhibition of the glucagon effect on cAMP, activation of phospholipase D. The fact that some of these effects can be selectively altered and that they are not, or differently, reproduced by some other analogues of ATP, suggests the presence of more than one receptor. (i) Pertussis toxin abolishes the anti-glucagon effect of ATP without affecting its glycogenolytic effect. (ii) Single cell calcium measurements reveal major differences between ATP and ADP, (iii) 2MeSATP and ADP beta S, in clear contrast to ATP, barely increase the levels of IP3 and their glycogenolytic effects is completely blocked by phorbol ester treatment of hepatocytes. (iv) 2MeSATP differs from ADP beta S since it has no anti-glucagon effect. 2. Effects of UTP on isolated hepatocytes so far do not show any difference with effects of ATP, suggesting interaction with the same receptor(s). 3. It is proposed that liver plasma membranes contain (at least) three different receptors mediating (a) the activation of phospholipase C, (b) the activation of phospholipase D and (c) the inhibition of adenylate cyclase.

摘要

三磷酸腺苷（ATP）对分离的肝细胞具有多种受体介导的效应：通过激活糖原磷酸化酶实现糖原分解（不依赖环磷酸腺苷（cAMP），由三磷酸肌醇（IP3）/钙介导）、糖原合酶失活、抑制胰高血糖素对cAMP的作用、激活磷脂酶D。这些效应中的一些能够被选择性改变，并且它们不能被ATP的某些其他类似物重现或被不同地重现，这表明存在不止一种受体。（i）百日咳毒素消除了ATP的抗胰高血糖素效应，而不影响其糖原分解效应。（ii）单细胞钙测量揭示了ATP和二磷酸腺苷（ADP）之间的主要差异，（iii）与ATP形成鲜明对比的是，2-甲硫基三磷酸腺苷（2MeSATP）和β-硫代二磷酸腺苷（ADPβS）几乎不增加IP3水平，并且它们的糖原分解效应在经佛波酯处理肝细胞后被完全阻断。（iv）2MeSATP与ADPβS不同，因为它没有抗胰高血糖素效应。2. 到目前为止，尿苷三磷酸（UTP）对分离的肝细胞的作用与ATP的作用没有任何差异，表明其与相同的受体相互作用。3. 有人提出肝细胞膜含有（至少）三种不同的受体，介导（a）磷脂酶C的激活、（b）磷脂酶D的激活和（c）腺苷酸环化酶的抑制。