The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis.
The apelin receptor (APJ; gene symbol APLNR) 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, which regulates fluid homeostasis, in the hypothalamic-pituitary-adrenal axis, which controls the neuroendocrine response to stress, and in the forebrain and lower brainstem regions, which are 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, as well as 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 related to altered water balance, stress-induced disorders such as anxiety and depression, and cardiovascular and metabolic disorders.
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK.
Anne-Marie
AM
O'Carroll
Stephen J
SJ
Lolait
Louise E
LE
Harris
George R
GR
Pope
D000595:Amino Acid Sequence; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D002319:Cardiovascular System / Q000187:drug effects; D002490:Central Nervous System / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009389:Neovascularization, Pathologic; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009765:Obesity; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000378:metabolism; D055503:Protein Multimerization; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution
C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D036341:Intercellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; D019001:Nitric Oxide Synthase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D048049:Extracellular Signal-Regulated MAP Kinases
APJ; G protein-coupled receptor; apelin; homeostasis