Modification by Cholecystokinin Octapeptide of the Binding ofμ‐, δ‐, and K‐Opioid Receptors

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Abstract
Previous study has shown that cholecystokinin (CCK) octapeptide (CCK-8) suppressed the binding of opioid receptors to the universal opioid agonist [3H]etorphine. In the present study, highly selective tritium-labeled agonists for the μ- {[tyrosyl-3,5-3H][d-Ala2,MePhe4,Gly-ol5]enkephalin ([3H]DAGO)}, δ- {[tyrosyl-3,5-3H][d-Pen2,5]enkephalin ([3H]DPDPE)}, and k- ([3H]U69,593) opioid receptors were used to clarify which type(s) of opioid receptor in rat brain homogenates is suppressed by CCK-8. In the competition experiments, CCK-8 suppressed the binding of [3H]DAGO and [3H]U69,593 but not that of [3H]DPDPE to the respective opioid receptor. This effect was blocked by the CCK antagonist proglumide at 1 μmol/L. In the saturation experiments. CCK-8 at concentrations of 0.1 nmol/L to 1 μmol/L decreased the Bmax of [3H]DAGO binding sites without affecting the KD; on the other hand, CCK-8 increased the KD of [3H]U69,593 binding without changing the Bmax. The results suggest that CCK-8 inhibits the binding of μ- and K-opioid receptors via the activation of CCK receptors.