Morphine noncompetitively inhibits [3H]leucine enkephalin binding to membranes lacking type-II delta binding sites: evidence for a two-site allosteric model.

Using the site-directed, delta-selective alkylating agent FIT (Rice et al., Science 220, 314-316, 1983), membranes devoid of detectable higher affinity delta binding sites were prepared. As compared to control membranes, the IC50 of morphine required to inhibit [3H]LE binding to FIT-treated membranes was two orders of magnitude lower. Further, morphine was a noncompetitive inhibitor of [3H]LE binding to FIT-treated membranes, supporting the notion that the lower affinity delta binding site is the delta binding site of the opiate receptor complex.