Differential inhibitory/stimulatory modulation of spinal CCK release by μ and δ opioid agonists, and selective blockade of μ-dependent inhibition by κ receptor stimulation

Opioid-cholecystokinin (CCK) interactions at the spinal level were investigated by looking for possible modulations by various opioid agonists of the release of cholecystokinin-like material (CCKLM) from slices of the dorsal zone of the rat lumbar enlargement. K +-evoked CCKLM overflow was reduced by 0.1–10 μM of the μ agonist DAGO or 10 nM to 3 μM of the δ agonist DTLET. By contrast, at a higher concentration (10 μM), the latter drug as well as morphine enhanced CCKLM overflow. Although inactive alone, the κ opioid agonist U 50488 H (1 μM) prevented the inhibitory effect of DAGO without affecting that of DTLET. These data suggest that an opioid acting through the stimulation of μ, δ and κ receptors (such as morphine) should produce a net increase in the spinal release of CCK.