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 mu 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 Y(130), M(132), G(133), T(134) within the first and F(315) within the third extracellular segment were required for antibody binding and conferred to IgG a high mu-opioid selectivity.
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