Cholecystokinin octapeptide reverses mu-opioid-receptor-mediated inhibition of calcium current in rat dorsal root ganglion neurons.

Cholecystokinin octapeptide (CCK-8) is reported to antagonize the analgesic effect produced by mu- and kappa- but not delta-opioid agonist in spinal cord. However, the mechanisms of interaction remain obscure. In the present study, whole-cell patch-clamp recording was performed on acutely isolated rat dorsal root ganglion (DRG) neurons to evaluate the effects of the highly specific mu-opioid agonist ohmefentanyl and the delta-opioid agonist DPDPE on voltage-gated calcium channels and the possible interaction between CCK-8 receptor and mu- or delta-opioid receptor. The results indicated that ohmefentanyl, but not DPDPE, can suppress the voltage-gated calcium currents elicited in DRG neurons, an effect readily reversed by naloxone or by the antiopioid peptide CCK-8. The effect of CCK-8 can in turn be abolished by the CCK-B receptor antagonist L365,260. CCK-8 used by itself has no enhancing effect, but rather a depressant effect, on calcium currents. However, used simultaneously with ohmefentanyl, CCK-8 shows a clear-cut reversal of depression of the mu-opioid. We conclude that the depressant effect produced by mu-opioid on voltage-gated calcium current in DRG neurons can be antagonized by CCK-8 through CCK-B receptor located in the same neuron. The delta-opioid DPDPE has no direct effect on the voltage-gated calcium current in DRG neurons.