Hydroxycarboxylic acid receptor 1 (HCA1), formerly known as G protein-coupled receptor 81 (GPR81), is a protein that in humans is encoded by the HCAR1 gene. HCA1, like the other hydroxycarboxylic acid receptors HCA2 and HCA3, is a Gi/o-coupled G protein-coupled receptor (GPCR). The primary endogenous agonist of HCA1 is lactic acid (and its conjugate base, lactate). More recently, 3,5-dihydroxybenzoic acid has been reported to activate HCA1.
Lactate was initially found to activate HCA1 on fat cells and thereby to inhibit these cells lipolysis i.e., break-down of their fats into free fatty acids and glycerol. Subsequent studies have found that in addition to fat cells, HCA1 is expressed on cells in the brain, skeletal muscle, lymphoid tissue, uterus, kidney, liver, and pancreas as well as on immune cells such as macrophages and antigen-presenting cells. In the brain, HCA1 acts to dampen neuron excitation and may also function to promote neurogenesis (i.e., production of neurons from neural stem cells) and angiogenesis, i.e., formation of new blood vessels from pre-existing blood vessels). The functions of HCA1 in non-fat and non-neural tissues have not been fully defined but in many cases appear to involve promoting the survival of cells, including various types of cancer cells.
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