Mu and delta opioids but not kappa opioid inhibit voltage-activated Ba2+ currents in neuronal F-11 cell.
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.
Nah
S Y
SY
Department of Physiology, School of Veterinary Medicine, Chonnam National University, Kwangju, South Korea. synah@chonnam.chonnam.ac.kr
Unteutsch
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Bunzow
J R
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Cook
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SP
Beacham
D W
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Grandy
D K
DK
D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006822:Hybrid Cells / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011957:Receptors, Opioid / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D000700:Analgesics; D000701:Analgesics, Opioid; D002121:Calcium Channel Blockers; D004745:Enkephalins; D010455:Peptides; D012333:RNA, Messenger; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013439:Sulfhydryl Reagents; D010566:Virulence Factors, Bordetella; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D001464:Barium; D020881:Enkephalin, D-Penicillamine (2,5)-; D020866:omega-Conotoxin GVIA; D037342:Pertussis Toxin; D005033:Ethylmaleimide; D002118:Calcium