Effects of adenosine receptor antagonism on protein tyrosine phosphatase in rat skeletal muscle

Earlier studies have shown that whole body adenosine receptor antagonism in creases skeletal muscle insulin sensitivity in insulin-resistant Zucker rat s. To find which steps in the insulin signaling pathway are influenced by a denosine receptors, muscle from lean and obese Zucker rats, treated for I w eek with the adenosine receptor antagonist, 1,3-dipropyl-8-(4-acrylate)-phe nylxanthine (BWA1433), were analyzed. All rats were first anesthetized and injected intravenously (i.v.) with 1 IU of insulin. About 3 min later the g astrocnemius was freeze clamped. Insulin receptors were partially purified on wheat germ agglutinin (WGA) columns and insulin receptor kinase activity measured in control and BWA1433-treated lean and obese Zucker rats. Protei n tyrosine phosphatase (PTPase) activity was also analyzed in subcellular f ractions, including the cytosolic fraction, a high-speed particulate fracti on and the insulin receptor fraction eluted from WGA columns. Administratio n of BWA1433 increased insulin receptor kinase activity in obese but not le an Zucker rats. PTPase activities were higher in the untreated obese rat mu scle particulate fractions than in the lean rat particulate fractions. The BWA1433 administration lowered the PTPase activity of the obese rats but no t the lean rats. Although the PTPase activity in WGA eluate fractions conta ining crude insulin receptors were similar in lean and obese animals, BWA14 33 administration was found to lower the PTPase activities in the fractions obtained from obese but not from the lean rats. PTPases may be upregulated in muscles from obese rats due to activated adenosine receptors. Adenosine receptor blockade, by reducing PTPase activity, may thereby increase insul in signaling. (C) 2001 Elsevier Science Ltd. All rights reserved.