Second Messenger Systems in the Brain

Abstract

About 25 years ago, Sutherland and his colleagues made an important discovery. Epinephrine and glucagon, acting as hormones, were both known to be able to profoundly affect the activity of the liver phosphorylase that catalyzes the conversion of glycogen to glucose 1-phosphate. Sutherland and Rail (1958), however, noted that the hormonal stimulation of phosphorylase activity did not take place in a medium that was devoid of the enzyme adenylate cyclase. Continuing studies demonstrated that the action of epinephrine and glucagon was directly on this enzyme rather than on the kinase that was responsible for the generation of liver phosphorylase (Fig. 15.1). What was happening was that the hormones were stimulating adenylate cyclase to convert ATP into cyclic adenosine 3‵, 5‵ monophosphate (cyclic AMP or cAMP). This cyclic AMP then triggered a phosphorylase kinase to activate the liver phosphorylase by attaching to it a phosphate group from a donor ATP.