Abstract

The apelin receptor (APJ) is a member of the G protein-coupled receptor gene family. Neural gene expression patterns of APJ, and its cognate ligand apelin, in the brain implicate the apelinergic system in the regulation of a number of physiological processes. APJ and apelin are highly expressed in the hypothalamo-neurohypophysial system that regulates fluid homeostasis, in the hypothalamic-pituitary-adrenal axis that controls the neuroendocrine response to stress, and in forebrain and lower brainstem regions involved in cardiovascular function. Recently, apelin, synthesised and secreted by adipocytes, has been described as a beneficial adipokine related to obesity, and there is growing awareness of a potential role for apelin, and APJ, in glucose and energy metabolism. In this review we provide a comprehensive overview of the structure, expression pattern, and regulation of apelin and its receptor, including the main second messengers and signalling proteins activated by apelin. We also highlight the physiological and pathological roles that support this system as a novel therapeutic target for pharmacological intervention in treating conditions relating to altered water balance, stress-induced disorders such as anxiety and depression, and cardiovascular and metabolic disorders.