CHARACTERIZATION OF THE BIOLOGICAL EFFECTS OF 2-METHYLTHIO-ATP ON RAT HEPATOCYTES - CLEAR-CUT DIFFERENCES WITH ATP

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 (K(a) 0.5-0.8-mu-M). This strong glycogenolytic potency of 2MeSATP suggests on its own the presence of P2Y-purinoceptors in liver. 2 Displacement of the radioligand ATP-alpha[S-35] 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[S-35] 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.