Abstract
Whole-cell patch-clamp recordings were used to study Ba2+ currents through voltage-dependent Ca2+ channels in dorsal root ganglion x mouse neuroblastoma hybrid (F-11) cells. Opioid agonists selective for either mu (Tyr-D-Ala-Gly-Mephe-Gly-ol; DAMGO) or delta (Tyr-D-Pen-Gly-Phe-D-Pen-OH; DPDPE) receptors inhibited high-threshold Ba2+ currents. The inhibition was reversible, naloxone-sensitive, and dose-dependent. The inhibitory effects of both DAMGO and DPDPE were blocked by pretreatment of the cells with pertussis toxin (PTX) as well as by brief exposure to the sulfhydryl alkylating agent, N-ethylmaleimide (NEM). The N-type Ca2+ channel antagonist omega-conotoxin GVIA (omega-CTX GVIA) irreversibly inhibited high threshold Ba2+ currents by 66% and blocked the inhibitory effect of DAMGO or DPDPE. In contrast, the L-type Ca2+ channel blocker nifedipine inhibited high threshold Ba2+ currents by 15% and failed to block the inhibitory effect of DAMGO or DPDPE. These results demonstrate that mu and delta opioid receptors are negatively coupled to N-type Ca2+ channels via PTX- and NEM-sensitive GTP-binding proteins in F-11 cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Analgesics / pharmacology
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Analgesics, Opioid / pharmacology
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Animals
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Barium / metabolism*
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Barium / pharmacology
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Calcium / metabolism
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Calcium Channel Blockers / pharmacology
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Dose-Response Relationship, Drug
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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Enkephalin, D-Penicillamine (2,5)-
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Enkephalins / pharmacology
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Ethylmaleimide / pharmacology
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Gene Expression Regulation / drug effects
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Hybrid Cells / chemistry
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Hybrid Cells / drug effects
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Hybrid Cells / physiology*
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Ion Channel Gating / drug effects
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Mice
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Neuroblastoma
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Patch-Clamp Techniques
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Peptides / pharmacology
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Pertussis Toxin
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RNA, Messenger / analysis
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Rats
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Receptors, Opioid / agonists
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Receptors, Opioid / genetics
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Receptors, Opioid / metabolism*
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Receptors, Opioid, delta / agonists
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Receptors, Opioid, delta / genetics
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Receptors, Opioid, delta / metabolism
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Receptors, Opioid, kappa / agonists
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Receptors, Opioid, kappa / genetics
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Receptors, Opioid, kappa / metabolism
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Receptors, Opioid, mu / agonists
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Receptors, Opioid, mu / genetics
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Receptors, Opioid, mu / metabolism
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Sulfhydryl Reagents / pharmacology
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Virulence Factors, Bordetella / pharmacology
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omega-Conotoxin GVIA
Substances
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Analgesics
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Analgesics, Opioid
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Calcium Channel Blockers
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Enkephalins
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Peptides
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RNA, Messenger
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Receptors, Opioid
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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Receptors, Opioid, mu
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Sulfhydryl Reagents
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Virulence Factors, Bordetella
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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Barium
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Enkephalin, D-Penicillamine (2,5)-
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omega-Conotoxin GVIA
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Pertussis Toxin
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Ethylmaleimide
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Calcium