Hydroxycarboxylic acid receptor 1

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 G_i/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.