Interconverting mu and delta forms of the opiate receptor in rat striatal patches.

Abstract

The binding of a radiolabeled .mu. receptor prototype opiate, dihydromorphine (H2morphine), and the binding of a .delta. receptor prototype, [D-Ala2, D-Leu5]enkephalin (D-Enk), to slide-mounted rat caudate slices were simultaneously compared quantitatively and visualized by autoradiography. Generally, D-Enk bound to opiate receptors distributed evenly throughout the entire striatum (type 2 pattern), whereas H2morphine labeled discrete islands or patches of receptors (type 1 pattern). In the presence of Mn2+ (3 mM) or other divalent cations Na+ and GTP at 25.degree. C caused an increase in D-Enk binding at the expense of H2morphine binding at striatal opiate receptor patches. These conditions shifted D-Enk binding from an even pattern to one that included both an even and patchy distribution. These incubation conditions not only promoted D-Enk binding to striatal patches but also enabled the opiate receptor to regulate adenylate cyclase with the same (P < 0.01) ligand selectivity pattern as that obtained by the displacement of D-Enk binding. The relative affinity of opiate receptors in striatal patches for opiate peptides, naloxone, and morphine appear to be a function of incubation conditions and coupling to adenylate cyclase and is not indicative of distinctly different opiate receptors. A 3-state allosteric model was postulated consisting of .mu. agonist, .mu. antagonist and adenylate cyclase-coupled .delta.-agonist-preferring states, whose equilibrium may be regulated by a sulfhydryl group mechanism.