Identification of μ-Opioid Receptor Epitopes Recognized by Agonistic IgG

We have previously reported the presence of IgG antibodies with a morphine-like activity in the serum of healthy individuals. The agonistic activity of IgG was dependent on their binding to the first and the third extracellular loops of the human μ opioid receptor. In this study we show that IgG antibodies obtained by immunizing rats with peptides corresponding to these two loops exhibited a similar morphine-like activity. Residues corresponding to Y130, M132, G133, T134 within the first and F315 within the third extracellular segment were required for antibody binding and conferred to IgG a high μ-opioid selectivity.