Adrenomedullin and PAMP: discovery, structures, and cardiovascular functions

We discovered adrenomedullin (AM) from human pheochromocytoma tissue by monitoring the elevating activity of intracellular cyclic AMP (cAMP) in rat platelets in 1993. Since the discovery of AM, it has attracted intense interest from cardiovascular researchers because AM elicits multiple biological activities, including a potent and powerful hypotensive activity caused by dilatation of resistance vessels. AM is biosynthesized and secreted from tissues, including cardiovascular organs. In addition to AM, "proadrenomedullin N-terminal 20 peptide (PAMP)," another biologically active peptide, was found to be processed from the AM precursor. Plasma AM levels are increased in various cardiovascular and renal diseases. AM, therefore, seems to function as a novel system that controls circulation and body fluid, and may be involved in pathophysiological changes in cardiovascular diseases. Therefore, in this review we will focus on the structure of AM and its gene, distribution, receptor, and the physiological and pathological roles of AM in cardiovascular disease.