Table 1.

Main characteristics of lactate-activated and proton sensor receptors in inflammatory response.

Receptor	Ligand	Location	G protein	Biological Function
HCA2, PUMA-G, HM74A or GPR109A.	Lactate	White and brown adipose tissue, macrophages, neutrophils, Langerhans epidermal cells, dendritic cells, and microglia.	Gαi/Gαo	Inhibition of NF-κB and reduction cytokine expression and apoptosis through BAD. Promotion to M2-like polarization of macrophages.
HCA1 or GPR81	Lactate	Adipocytes, macrophages monocytes, endothelial cells	Gαi	Inhibition of lipolysis in adipocytes. Inhibition of NLRP3 inflammasome release by activating the intracellular adaptor protein, β-arrestin 2 (ARRB2), and attenuating NF-κB activity. Increased vascular permeability inducing the mobilization of bone marrow (BM) neutrophils.
GPR4	Proton sensor	Vascular endothelial cells.	Gαs	Induces NF-κB activation and increases the inflammatory response in endothelial cells. Activates apoptotic pathways and regulates the endoplasmic reticulum (ER) stress in endothelial cells.
GPR65 or TDAG8	Proton sensor	T cells, B cells, neutrophils, and eosinophils.	Gαs	Reduces pro-inflammatory cytokine production (TNF-α and IL-6), ROS production and apoptosis.
GPR132 or G2A	Proton sensor	Macrophages and neutrophils.	Gαq	Promotes activation of the peroxisome proliferator-activated receptor γ (PPARγ) in tumor-associated macrophages (TAMs) causing activation to macrophage M2 and tumor growth.
GPR68 or OGR1	Proton sensor	Macrophages, dendritic cells, T cells and neutrophils.	Gαq/11 and Gαs	Maintain tumor-associated macrophages in an M2-like state and suppresses T-cell infiltration favoring tumor growth. Increases the production of CXCL8 and IL-6 in human airway smooth muscle cells related to bronchial contraction and hyperresponsiveness of the airways in patients with bronchial asthma.