Pharmacological evidence for the involvement of calcium/calmodulin in serotonin 5-HT3 receptor-mediated cation permeability in NG 108-15 cells.
In NG 108-15 clonal cells, extracellular application of micromolar concentrations of serotonin [5-hydroxytryptamine (5-HT)] and substance P induces the opening of a cation permeability monitored by the influx of [14C]-guanidinium. The serotoninergic component of this cation permeability is linked to 5-HT3 receptor activation, whereas the substance P component probably involves an "N-terminal-dependent substance P receptor." In this study, [14C]guanidinium influx triggered by 1 microM 5-HT plus 10 microM substance P was shown to be insensitive to tetrodotoxin, verapamil, diltiazem, nimodipine, and omega-conotoxin, as expected from a process independent of voltage-sensitive sodium and calcium channels. In contrast, [14C]guanidinium influx was inhibited by millimolar concentrations of extracellular calcium and by the chelation of intracellular calcium by bis-O-aminophenoxyethanetetraacetic acid. The inhibition by extracellular calcium apparently involved a competition between the divalent cation and [14C]guanidinium for the same channel. When NG 108-15 cells were exposed to X537A, an ionophore that specifically induces release of calcium from intracellular stores, [14C]guanidinium uptake was markedly increased even in the absence of 5-HT and/or substance P. Conversely, [14C]guanidinium influx due to the latter substances could be reversibly and dose-dependently blocked by various drugs that possess calmodulin-antagonizing properties. These results strongly suggest that the cation permeability opened by 5-HT and substance P in NG 108-15 cells involves a calcium/calmodulin-dependent process.(ABSTRACT TRUNCATED AT 250 WORDS)
Riad
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INSERUM U288, Neurobiologie Cellulaire et Fonctionnelle, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Hamon
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Emerit
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D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D002412:Cations / Q000378:metabolism*; D002463:Cell Membrane Permeability; D000242:Cyclic AMP / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D019791:Guanidine; D006146:Guanidines / Q000493:pharmacokinetics; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D026941:Sodium Channel Blockers; D014407:Tumor Cells, Cultured
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002121:Calcium Channel Blockers; D002147:Calmodulin; D002412:Cations; D006146:Guanidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D026941:Sodium Channel Blockers; D009569:Nitric Oxide; C055971:zacopride; D000242:Cyclic AMP; D011493:Protein Kinase C; D019791:Guanidine; D002118:Calcium