Activation of protein kinase(s) by glucagon and cyclic AMP in the rat liver. Relationship to metabolic effects.
Although it is known that protein kinases are activated by cyclic AMP, the role of the activated kinase in the gluconeogenic response to cyclic AMP is not known. Therefore, we examined whether the inhibition of the gluconeogenic response in the liver is due to an interference with the activation of protein kinase in the following situations: (1) adrenalectomy, (2) Na+-free perfusate, (3) administration of local anesthetic. We measured protein kinase activity indirectly by measuring incorporation of 32P into proteins of the perfused liver, and directly by measuring the enzyme activity. We found no significant inhibition of activation of protein kinase in the above experimental conditions. It seems that in the intact liver, activation of protein kinase by itself is not sufficient to evoke metabolic responses. In order to clarify whether the requirement for ion redistribution is specific for the gluconeogenic response or not, the lipolytic and antilipogenic effects of glucagon and cyclic AMP were examined. Na+-free perfusate, local anesthetic or high K+ did interfere with the lipolytic and antilipogenic responses to these agents just as it interfered with the gluconeogenic response. It is likely that ion redistribution evoked by glucagon and cyclic AMP is essential to the expression of most, if not all, metabolic effects.
D000315:Adrenalectomy; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D010477:Perfusion; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D013748:Tetracaine / Q000494:pharmacology
D013748:Tetracaine; D005934:Glucagon; D012964:Sodium; D000242:Cyclic AMP; D011494:Protein Kinases; D006152:Cyclic GMP; D002118:Calcium