Cholecystokinin octapeptide reverses the kappa-opioid-receptor-mediated depression of calcium current in rat dorsal root ganglion neurons

Abstract

Although the cholecystokinin octapeptide (CCK-8) is reported to antagonize the kappa-opioid-receptor-mediated analgesic effect in spinal cord, its mechanism and sites of action remain obscure. In the present study, the whole-cell patch-clamp recording technique was employed to examine the effect of kappa-opioid agonist U50488H on voltage-gated calcium channels and the interaction between the CCK-8 and U50488H in acutely isolated rat dorsal root ganglion neurons. The results indicate that the calcium currents elicited in dorsal root ganglion neurons can be depressed by U50488H, an effect readily reversed by the kappa-opioid receptor antagonist Nor-BNI or by the antiopioid peptide CCK-8. The effect of the CCK-8 can be abolished by the CCK-B receptor antagonist, L365,260. While CCK-8 showed a potent opioid-reversal effect, it by itself exerted a slight inhibitory effect on calcium current. This novel observation in the dorsal root ganglion neurons indicates that CCK-8 can antagonize the kappa-opioid-receptor-mediated depressant effect on voltage-gated calcium current, and this antagonizing effect appears to be mediated via CCK-B receptor.