Cell and molecular biology of the multifunctional peptide, adrenomedullin

Adrenomedullin (AM) is a recently discovered regulatory peptide involved in many functions including vasodilatation, electrolyte balance, neurotransmission, growth, and hormone secretion regulation, among others. This 52-amino acid peptide is expressed by specific cell types in many organs throughout the body. A complex receptor system has been described for AM; it requires at least the presence of a seven-transmembrane-domain G-protein-coupled receptor, a single-transmembrane-domain receptor activity modifying protein, and a receptor component protein needed to establish the connection with the downstream signal transduction pathway, which usually involves cyclicAMP. In addition, a serum-binding protein regulates the biological actions of AM, frequently by increasing AM functional attributes. Changes in levels of circulating AM correlate with several critical diseases, including cardiovascular and renal disorders, sepsis, cancer, and diabetes. Whether AM is a causal agent, a protective reaction, or just a marker for these diseases is currently under investigation. New technologies seeking to elevate and/or reduce AM levels are being investigated as potential therapeutic avenues.