Modulation of μ‐opioid receptor activation by acidic pH is dependent on ligand structure and an ionizable amino acid residue

Abstract

Our investigations indicate that low pH selectively impairs μ-opioid receptor signalling modulated by ligands capable of forming hydrogen bonds with H297^6.52 . We propose that protonation of H297^6.52 at acidic pH reduces binding and subsequent signalling of such ligands. Novel agonists targeting opioid receptors in injured tissue might benefit from lack of hydrogen bond formation with H297^6.52 .