Binding to mu and delta opioid sites but not kappa sites is inhibited by Fab fragments from a monoclonal antibody directed against the opioid receptor.

Fab fragments from a monoclonal antibody, OR-689.2.4, directed against the opioid receptor selectively inhibited opioid binding to rat and guinea pig neural membranes. In a titrable manner, the Fab fragments noncompetitively inhibited the binding of the mu selective peptide, [3H][D-Ala2, MePhe4, 2Gly-ol5] enkephalin (DAGO) and the delta selective peptide, [3H][D-Pen2, D-Pen5] enkephalin (DPDPE), to neural membranes. The binding of [125I-Tyr27] beta-endorphin was also blocked by the Fab fragments. In contrast, kappa opioid binding, as measured by the binding of [3H]bremazocine to rat neural membranes and guinea pig cerebellum in the presence of mu and delta blockers was not significantly altered by the Fab fragments. When mu sites were blocked with DAGO, the Fab fragments suppressed the binding of [3H]DPDPE to the same degree as when the mu binding sites was not blocked. The Fab fragments also inhibited binding to the mu site regardless of whether or not the delta site was blocked. This monoclonal antibody is directed against a 35,000 dalton protein. Since the antibody is able to inhibit mu and delta binding but not kappa opioid binding, it appears that the 35,000 dalton protein is an integral component of mu and delta opioid receptors but not kappa receptors.