CYCLIC-AMP RESPONSE TO GLUCAGON - COMPARISON OF TISSUE AND PLASMA CYCLIC-AMP LEVELS IN RABBIT

The effects of glucagon on tissue and plasma cyclic[c]AMP levels were investigated in rabbits anesthetized with urethane. Glucagon (2 nmol/kg) caused at least a 2-fold increase in hepatic cAMP, which reached a peak within 2 min and declined to basal values after 40 min. Plasma cAMP also increased at least 2-fold, reaching a peak at 10 min and declining to basal values after 60 min. Glucagon (20 nmol/kg) stimulated hepatic and plasma cAMP in a manner indistinguishable from that observed at the lower dose. Hepatectomy abolished the plasma cAMP responses to glucagon, and no significant stimulation of cAMP concentration was noted in the heart, adipose tissue, small bowel or kidney. cAMP hydrolysis was estimated in blood taken before and after administration of glucagon. Glucagon (2 nmol/kg) increased cAMP hydrolysis slightly, but this was explained by the raised cAMP levels. cAMP hydrolysis increased 2- to 3-fold in blood taken 20 and 40 min after glucagon (20 nmol/kg). The higher dose of glucagon also stimulated cAMP hydrolysis in crude liver homogenate, which could not be explained by increases in cAMP concentration. The increase in cAMP hydrolysis observed in blood and liver may partly explain the failure to show additional stimulation of hepatic and plasma cAMP levels with the higher dose of glucagon. Despite the changes in cAMP hydrolysis, a highly significant correlation was observed in individual rabbits between the hepatic and plasma cAMP responses to glucagon (2 and 20 nmol/kg), when these were calculated as incremental areas above mean basal levels. Measurement of plasma cAMP levels after stimulation by glucagon may be an accurate index of the hepatic cAMP response to glucagon in vivo.