glutaminase and adenosine-3--5--cyclic-phosphorothioate

(1) Glucagon activates hepatic glutaminase in vivo. Mitochondria from glucagon-injected rats retain an enhanced capacity to catabolize glutamine and this is more sensitive to activation by inorganic phosphate. The glucagon-elicited stimulation of glutaminase is not evident in broken mitochondria. A similar activation of glutaminase occurs in a number of situations which are associated with elevated glucagon levels in vivo, i.e., after a high-protein meal, after injection of bacterial endotoxin and in diabetes mellitus. (2) Studies in isolated hepatocytes revealed that glutaminase could be activated, not only by glucagon, but also by a cell-permeable protein kinase A activator (Sp-cAMPS) and by a cell-permeable protein phosphatase 1 and 2A inhibitor (okadaic acid). However, the activation of glutaminase by glucagon was not inhibited by a cell-permeable protein kinase A inhibitor (Rp-8-Br-cAMPS). We suggest that the signalling pathway, for glutaminase activation by glucagon, is complex and possibly contains redundant elements.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Animals; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Diabetes Mellitus, Experimental; Dietary Proteins; Endotoxins; Enzyme Activation; Enzyme Inhibitors; Ethers, Cyclic; Glucagon; Glutamic Acid; Glutaminase; Glutamine; Mitochondria, Liver; Okadaic Acid; Phosphates; Rats; Signal Transduction; Thionucleotides