Inhibition of the omega-conotoxin-sensitive calcium current by distinct G proteins.
Leu-enkephalin (Leu-Enk), norepinephrine (NE), somatostatin (SS), and bradykinin (BK) decrease the voltage-dependent calcium current in NG108-15 cells. Here we have investigated whether distinct G proteins, or a G protein common to all of the pathways, mediates this inhibition. We found that pertussis toxin (PTX) reduced all of these transmitter actions, except that of BK. To examine which of the PTX-sensitive pathways is transduced by GoA, we constructed an NG108-15 cell line that stably expresses a mutant, PTX-resistant alpha subunit of GoA. After treatment with PTX, the mutant GoA alpha rescued the Leu-Enk and NE pathways but not the SS pathway. At least three different G proteins can transduce receptor-mediated inhibition of calcium currents in nerve cells. The effects of these G proteins appear to converge on the omega-conotoxin GVIA-sensitive calcium current.
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235.
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Taussig
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Sanchez
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Rifo
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Gilman
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Belardetti
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004743:Enkephalin, Leucine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D008564:Membrane Potentials; D016297:Mutagenesis, Site-Directed; D009638:Norepinephrine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D037342:Pertussis Toxin; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D015220:Calcium Channels; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D010566:Virulence Factors, Bordetella; D013004:Somatostatin; D004743:Enkephalin, Leucine; D004247:DNA; D020866:omega-Conotoxin GVIA; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D001920:Bradykinin; D009638:Norepinephrine