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.
Neuroscience Research Center, Beijing Medical University, China.
N J
NJ
Liu
T
T
Xu
C
C
Xu
C Q
CQ
Li
Y X
YX
Yu
H G
HG
Kang
J S
JS
Han
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D005283:Fentanyl / Q000031:analogs & derivatives / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015640:Ion Channel Gating; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000502:physiology; D012844:Sincalide / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D004745:Enkephalins; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C037016:F 7302; D020881:Enkephalin, D-Penicillamine (2,5)-; D012844:Sincalide; D005283:Fentanyl