ATP and other nucleoside triphosphates inhibit the binding of insulin to its receptor.
ATP, in a dose-dependent manner, inhibited the binding of 125I-insulin to its receptor in rat liver and human placental membranes. With rat liver plasma membranes an effect of ATP was detected at concentrations between 1.0 and 2.5 mmol/L, and maximal effects were seen at 10.0 mmol/L where binding was decreased by approximately 40%. The effect of ATP was one half-maximal within 10 minutes and maximal within 60 minutes. Scatchard analysis indicated that ATP was acting primarily to change the binding affinity of the insulin receptor. The effect of ATP was mimicked by CTP, GTP, and UTP, but not by ADP, 5'-AMP, 3'-AMP, 3'5'-cyclic AMP and adenosine. The ATP analog AMP-PNP had a potency approximately 10% that of ATP. The effect of ATP was not significantly influenced by inhibitors of phosphoprotein kinases and phosphoprotein phosphatases. In human placental membranes, ATP had a similar effect in inhibiting 125I-insulin binding to its receptor. Moreover, ATP was active in inhibiting insulin binding to purified human placental insulin receptors at 0.01 mmol/L, a concentration 1/100 of that needed for inhibiting binding to intact membranes. These studies indicate, therefore, that ATP and other nucleoside triphosphates influence the ability of the insulin receptor to bind insulin.
D000249:Adenosine Monophosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003570:Cytidine Triphosphate / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D009711:Nucleotides / Q000494:pharmacology*; D010920:Placenta / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*
D007328:Insulin; D009711:Nucleotides; D000249:Adenosine Monophosphate; D003570:Cytidine Triphosphate; D000255:Adenosine Triphosphate; D011972:Receptor, Insulin