Characterization of the biological effects of 2-methylthio-ATP on rat hepatocytes: clear-cut differences with ATP

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Abstract
1. In several tissues, 2-methylthio adenosine triphosphate (2MeSATP) is a very potent P2y-purine agonist. In rat hepatocytes, 2MeSATP half-maximally activated glycogen phosphorylase at 20 nM and was therefore about 25 times more effective than ATP (Ka 0.5-0.8 microM). This strong glycogenolytic potency of 2MeSATP suggests on its own the presence of P2Y-purinoceptors in liver. 2. Displacement of the radioligand ATP alpha[35S] from its receptor however occurred at much higher concentrations of 2MeSATP than was anticipated on the basis of its glycogenolytic potency. 3. The interaction of 2MeSATP with the receptor, characterized with ATP alpha[35S] as radioligand, cannot be considered as a pure competitive interaction. 4. 2MeSATP did not share the ability of ATP to counteract the effect of glucagon on the adenosine 3':5'-cyclic monophosphate levels. 5. 2MeSATP barely increased the levels of inositol trisphosphate (IP3). 6. The glycogenolytic effect of 2MeSATP was completely abolished by pretreatment of the hepatocytes with phorbol myristic acetate. 7. It is tentatively concluded that 2MeSATP and ATP are interacting with different P2 purinoceptors.