Effect of glucagon, dibutyryl adenosine 3',5'-cyclic monophosphate and phosphodiesterase inhibitors on rat liver phosphorylase activity and adenosine 3',5'-cyclic monophosphate levels

Theophylline, papaverine and 1-ethyl-4-(isopropylidenehydrazine)-1H-pyrazole-(3,4-b)-pyridine-5-carboxylic acid, ethyl ester HCl (SQ 20,009) were found to inhibit both high K_m (200 μM) and low K_m(3 μM) cyclic 3′,5′-AMP phosphodiesterase activity in 100,000 g supernatant fraction from rat liver. Theophylline was the least potent and SQ 20,009 the most potent inhibitor of both activities. In the liver slice preparation, papaverine (5 × 10^?4), theophylline (10^?3 M) and SQ 20,009 (10^?3 M) failed to elevate cyclic 3′,5′-AMP, while glucagon (10^?6 M) produced a significant (P < 0·05) elevation in the tissue levels of the cyclic nucleotide. All three phosphodiesterase inhibitors significantly (P < 0·05) augmented the ability of glucagon to elevate cyclic 3′,5′-AMP levels. Glucagon and papaverine stimulated phosphorylase activity, while theophylline inhibited both basal and glucagon-stimulated phosphorylase activity. SQ 20,009 was without effect. It is concluded that no cause and effect relationship can be assumed between an ability to inhibit phosphodiesterase and to alter phosphorylase activity.