Free fatty acid 2 receptor regulates the NADPH oxidase activity induced by formyl peptide receptor specific agonists
The neutrophil NADPH oxidase is activated by signals generated by formyl peptide receptor (FPR) agonists recognized by FPR1 (fMLF) and FPR2 (WKYMVM), respectively. Also, the antagonists cyclosporin H (specific for FPR1) and PBP10 (specific for FPR2) inhibit the NADPH oxidase activity when induced by the two peptide agonists. When bound to its receptor, the non-activating positive allosteric…
The NADPH oxidase, a crucial enzyme in neutrophil function, is activated by specific signals generated by formyl peptide receptor (FPR) agonists. Two types of FPRs, FPR1 and FPR2, are recognized by their respective agonists fMLF and WKYMVM. Conversely, antagonists cyclosporin H and PBP10 inhibit NADPH oxidase activity upon stimulation by these peptide agonists.
Interestingly, a negative allosteric modulator, Cmp58, specific to free fatty acid 2 receptor (FFA2R), influences both FPR-induced responses and the activity of FPR agonists. Despite Cmp58 not affecting the efficacy of FPR-induced responses, it diminishes the inhibitory effect of the respective FPR antagonists. This altered sensitivity can be reversed by a specific FFA2R antagonist.
According to a receptor trans-regulation model, FPRs activate the NADPH oxidase directly through generated signals, while signals activating the allosterically modulated FFA2Rs also contribute to NADPH oxidase activation.
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