Description
GPR84 is a Gα
i protein-coupled receptor that is activated by medium-chain free fatty acids, but only at micromolar concentrations. GPR84 is expressed in leukocytes and its expression is further induced by LPS. 6-OAU is a synthetic agonist for GPR84 (EC
50 = 512 nM). It has insignificant actions at a panel of 69 other receptors, channels, or transporters. 6-OAU promotes chemotaxis in human neutrophils (EC
50 = 318 nM) and amplifies TNF-α production by LPS-treated U937 macrophages. In rats, 6-OAU (1 mg/ml) drives the recruitment of neutrophils and macrophages when injected into a subcutaneous air pouch and raises serum levels of CXCL1 (growth-regulated α protein) when delivered intravenously.
in vitro
a previous study identified 6-oau as a surrogate agonist for gpr84. it was found that 6-oau and potential ligands were able to stimulate [(35)s]gtp binding and accumulate phosphoinositides in a gpr84-dependent manner. moreover, 6-oau could internalize gpr84-egfp from the cell surface. in addition, results showed that both 6-oau and the potential ligands could elicite chemotaxis of human polymorphonuclear leukocytes (pmns) and macrophages and amplify lps-stimulated production of the proinflammatory cytokine il-8 from pmns and tnfα from macrophages [1].
in vivo
animal study found that the iv injection of 6-oau was able to raise the blood cxcl1 level in rats. in addition, the inoculation of 6-oau into the rat air pouch could accumulate pmns and macrophages in the site [1].
References
[1] suzuki, m. ,takaishi, s.,nagasaki, m., et al. medium-chain fatty acid-sensing receptor, gpr84, is a proinflammatory receptor. the journal of biological chemisty 288(15), 10684-10691 (2013).
