Nitric Oxide and Cyclic GMP in Cell Signaling and Drug Development

Abstract

As an M.D.–Ph.D. student, I was fortunate to have worked in the laboratories of Earl Sutherland and Theodore Rall shortly after their discovery of cyclic adenosine monophosphate (AMP) in 1957 as a second messenger that mediates the glycogenolytic effects of epinephrine and glucagon.¹ My assignment was to examine the effects of catecholamines on cyclic AMP synthesis and determine whether these effects were mediated through the beta or alpha adrenergic receptor. This was actually a straightforward and simple student assignment.² I also found that choline esters such as acetylcholine, acting by transduction at the muscarinic receptor, inhibited adenylyl cyclase activity.² This experience set the stage for my long-term continued interest in cellular signaling and the role of intracellular second messengers in mediating the effects of various hormones and drugs.