Role of adrenomedullin in human body

Adrenomedullin (AM), discovered in 1993, is a 52-amino acid vasoactive peptide with multi-functions associated with pheochromocytoma (a tumour arising from adrenal medulla). It is widely distributed in human tissues, especially in cardiovascular and endocrine tissues and is metabolized via aminopeptidase action. It has two specific receptors formed by the calcitonin-receptor-like receptor (CALCRL) and receptor activity-modifying protein (RAMP) 2 or 3 known as AM1 and AM2 receptors, respectively. In addition, it has appreciable affinity for the calcitonin gene-related peptide (CGRP1) receptor. At present adrenomedullin is believed to function through combinations of the CALCRL and RAMP2 complexes, as well as CGRP receptors. It is the most potent endogenous vasodilatory peptide found in the body. Its effects include increasing the tolerance of cells to oxidative stress and hypoxic injury and angiogenesis. It shows a positive influence in disorders such as hypertension, myocardial infarction, chronic obstructive pulmonary disease and other cardiovascular diseases. It acts as a local regulator of bone growth and has marked beneficial effects in the host defense mechanism. It increases blood flow in the adrenal gland, causing a gradual release of catecholamines. It is expressed and accumulated in epithelial surfaces (skin, lung, genitourinary tract, digestive system and others) and body fluids (plasma, sweat, milk, saliva, amniotic fluid and others) thereby illustrating its role as an antimicrobial agent. It has a protective role during sepsis and is rendered as an attractive molecule for the treatment of septic shock.