Visualization and solubilization of rat brain opiate receptors with a ??? ligand selectivity pattern

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Abstract
Specific binding of [3H]ethylketocyclazocine (EKC), a prototypeκ-opiate agonist, to slide-mounted rat striatal sections is increased in the presence of 100 mM NaCl at 4°C. Under similar incubation conditions, binding ofµ andδ prototype opiates is reduced to almost undetectable levels. Correlation (P < 0.01) of the ligand selectivity pattern of [3H]EKC displacement with the potencies of various opiate drugs in inhibiting the contractions of the rabbit vas deferens, aκ-opiate receptor bioassay, suggests that the binding site under study represents the pharmacologically relevantκ-opiate receptor. Visualization of theseκ-opiate receptors with tritium-sensitive film reveals a striking, highly discrete brain distribution pattern (e.g., striatal patches, habenular stripe) which is similar to that of [3H]dihydromorphine and [3H]naloxone. Soluble [3H]EKC binding sites obtained from rat membranes also possess aκ-like ligand selectivity pattern, with bremazocine being a potent displacer whileµ andδ ligands are almost inactive. A possible explanation of these data is that the “κ”-opiate binding site in rat brain is one transitional state of an opiate receptor capable of assuming distinct conformations with characteristic ligand selectivity patterns. Other possibilities such as pre and post-synaptic locations should also be considered.