Hydroxycarboxylic Acid Receptor 1 (HCAR1)

Hydroxycarboxylic Acid Receptor 1 (HCAR1), also known as GPR81 or lactate receptor 1, is a Class A G protein-coupled receptor primarily activated by lactate. It is highly expressed in adipose tissue and found at lower levels in other tissues including liver, kidney, muscle, brain and pituitary gland. HCAR1 is coupled to Gi/Go proteins, leading to inhibition of adenylyl cyclase and decreased cAMP levels. It plays a role in metabolic regulation by inhibiting lipolysis in adipocytes and modulates neural activity by downregulating neural excitability. HCAR1 is also implicated in cancer biology, promoting tumor proliferation, metastasis, angiogenesis, survival and immune evasion.

Other names

GPR81lactate receptor 1FKSG80LACR1T-cell activation G protein-coupled receptorG protein-coupled receptor 104

Activation of HCAR1 leads to inhibition of adenylyl cyclase, resulting in decreased intracellular cAMP levels and downstream effects such as reduced PKA activity. In neurons, it reduces excitatory presynaptic current frequency, decreases neuronal firing/spiking frequency, and modulates calcium signaling.