Effects of diadenosine triphosphate and diadenosine tetraphosphate on rat liver cells - Differences and similarities with ADP and ATP

Liver cells possess multiple types of purinoceptors that mediate the effects of extracellular nucleo tides. Like ADP and ATP, the dinucleotides diadenosine triphosphate (Ap(3)A) and diadenosine tetraphosphate (Ap(4)A) fully activated glycogen phosphorylase, with ED(50) values of 0.31 mu M and 1.3 mu M, respectively. At variance with ATP, neither the dinucleotides nor ADP significantly Increased the levels of IP3. Ap(4)A (and also ADP) moderately increased IP3 (+/-72%) whereas Ap(3)A was completely ineffective. Like ATP, Ap(3)A, Ap(4)A, and ADP inhibited the cAMP increase after glucagon. Phorbol-12-myristate-13-acetate (PMA) pretreatment of the hepatocytes clearly inhibited the glycogenolytic potency of Ap(3)A and ADP, but had only a minor effect on the potency of Ap(4)A or ATP. It is concluded that, depending upon the effect studied (glycogenolytic effect with or without PMA, increasing IP3 potency, or inhibition of cAMP increase), different analogies between the agonists studied emerged, indicating the complexity of the interaction of ATP and its analogues with liver purinoceptors and/or of the transduction mechanism(s) initiated by the different nucleotides.