MODIFICATION BY CHOLECYSTOKININ OCTAPEPTIDE OF THE BINDING OF MU-OPIOID, DELTA-OPIOID, AND KAPPA-OPIOID RECEPTORS

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. Copyright © 1990, Wiley Blackwell. All rights reserved