Opioid potentiation of N-type Ca2+ channel currents via pertussis-toxin-sensitive G proteins in NG108-15 cells.
Opioids have both inhibitory and stimulatory effects on neurotransmitter release. While the inhibitory effect has been ascribed to presynaptic inhibition of Ca2+ channels, the cellular mechanism underlying the stimulatory effect is not clear. In order to address this issue, we analyzed the effects of [d-Ala2, d-Leu5]-enkephalin (DADLE) on whole-cell Ba2+ currents (IBa) through voltage-gated Ca2+ channels in NG108-15 neuroblastoma x glioma hybrid cells. Application of DADLE inhibited and washout of DADLE transiently potentiated IBa. Furthermore, potentiation of IBa was elicited even in the presence of DADLE, when inhibition was relieved by a large depolarizing prepulse. DADLE-induced potentiation, as well as inhibition, had both voltage-sensitive and -insensitive components and was abolished by treatment with ICI174864, a delta-opioid antagonist, pertussis toxin (PTX) and omega-conotoxin GVIA. Potentiation developed over @3 min and took 5-20 min to recover, whereas inhibition was complete within 30 s and recovered within 1 min. Although this potentiation should contribute to DADLE-induced desensitization of Ca2+ channel inhibition, it was not the sole mechanism for desensitization. We conclude that the delta-opioid receptor exerts a dual action on N-type Ca2+ channels via PTX-sensitive G proteins, i.e., rapid inhibition followed by slowly developing potentiation.
Department of Anesthesia, Kyoto University Hospital, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. morikawa@ohsu.edu
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Morikawa
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Mima
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Uga
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Shoda
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Fukuda
D001464:Barium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology*; D004553:Electric Conductivity; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D005910:Glioma; D006822:Hybrid Cells; D007700:Kinetics; D009447:Neuroblastoma; D037342:Pertussis Toxin; D017465:Receptors, Opioid, delta / Q000502:physiology*; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D015220:Calcium Channels; D017465:Receptors, Opioid, delta; D010566:Virulence Factors, Bordetella; D001464:Barium; D016308:Enkephalin, Leucine-2-Alanine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins