Opioid receptor binding properties of analgesic analogues of cholecystokinin octapeptide.

Four analogues of cholecystokinin (CCK) octapeptide having analgesic activity after i.c.v. administration and high affinity for CCK-B receptors were studied for their ability to displace specific ligands, [3H]D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2. [3H][D-Pen2, 4'-Cl-Phe4,D-Pen5]enkephalin and [3H]U-69,593, for mu-, delta- and kappa-opioid receptors, respectively. None of the analogues tested have high affinity for either mu- or kappa-receptors (IC50 values greater than 0.7 microM), but their IC50 values for delta-receptors range from 29 to 1023 nM. The results suggest a relationship between the ligand requirements of CCK-B and delta-opioid receptors which further implies a possible structural relationship between these receptors.