The Effects of Adrenergic Blocking Agents and Theophylline on 3',5'-amp-induced Hyperglycemia.

It was reported that hyperglycemia may be elicited in the intact dog (Sutherland and Rail, 1960; Posternak ci at., 1962) and rat by administration of the cyclic nucleotide, 3’, 5’-AMP,4 in doses of 10 mg/kg and greater (Northrop and Parks, 1964a). Also, it was shown with the isolated perfused rat liver that hyperglycemia, glycogenolysis and a-glucan phosphorylase5 activation can be caused by perfusion with blood containing 3’, 5’-AMP. The lowest concentration of cyclic nucleotide that induced hyperglycemia with this preparation was 0.002 mg/ml of blood (Northrop and Parks, 1964a,b). The effects of 3’, 5’-AMP in tissues appear to be terminated by the action of a magnesium-activated phosphodiesterase that catalyzes hydrolysis at the 3’ position and forms adenosine 5’-phosphate (Sutherland and Rail, 1958; Drummond and Perrott-Yee, 1961; Butcher and Sutherland, 1962). This enzyme was found in many tissues and was inhibited by the methyl xanthines. Theophyiline was the most potent of the methyl xanthines tested; the inhibition was competitive