Unsulfated C-terminal 7-peptide of cholecystokinin: a new ligand of the opiate receptor.

On the basis of structural and conformational similarities between the C-terminal 7-peptide of cholecystokinin (pancreozymin) (CCK-(27–33)) and the active enkephalin analog Trp⁴,Met⁵]-enkephalin, the affinity of CCK-(27–33) for the opiate receptor was determined. With unsulfated CCK-(27–33) half-maximal inhibition of stereospecific binding of ³H]-naloxone in a rat brain membrane preparation was observed at a 200 times higher concentration than that required with Met⁵]-enkephalin. Sulfated CCK-(27–33) did not bind at concentrations up to 4 × 10^?5M. In the bioassay based on inhibition of electrically evoked contractions of guinea pig ileum similar potency ratios were observed and the effect of CCK-(27–33) was shown to be naloxone-reversible. These findings are of interest in view of the recently demonstrated presence of CCK-fragments in the brain.