DIFFERENTIAL INHIBITORY STIMULATORY MODULATION OF SPINAL CCK RELEASE BY MU-OPIOID AND DELTA-OPIOID AGONISTS, AND SELECTIVE BLOCKADE OF MU-DEPENDENT INHIBITION BY KAPPA-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-mu-M of the mu agonist DAGO or 10 nM to 3-mu-M of the delta agonist DTLET. By contrast, at a higer concentration (10-mu-M), the latter drug as well as morphine enhanced CCKLM overflow. Although inactive alone, the kappa opioid agonist U 50488 H (1-mu-M) prevented the inhibitory effect of DAGO without affecting that of DTLET. These data suggest that an opioid acting through the stimulation of mu, delta and kappa receptors (such as morphine) should produce a net increase in the spinal release of CCK.