title: A pertussis toxin-sensitive 8-lipoxygenase pathway is activated by a nicotinic acetylcholine receptor in aplysia neurons.
abstract: Acetylcholine (ACh) activates two types of chloride conductances in Aplysia neurons that can be distinguished by their kinetics and pharmacology. One is a rapidly desensitizing current that is blocked by alpha-conotoxin-ImI and the other is a sustained current that is insensitive to the toxin. These currents are differentially expressed in Aplysia neurons. We report here that neurons that respond to ACh with a sustained chloride conductance also generate 8-lipoxygenase metabolites. The sustained chloride conductance and the activation of 8-lipoxygenase have similar pharmacological profiles. Both are stimulated by suberyldicholine and nicotine, and both are inhibited by alpha-bungarotoxin. Like the sustained chloride conductance, the activation of 8-lipoxygenase is not blocked by alpha-conotoxin-ImI. In spite of the similarities between the metabolic and electrophysiological responses, the generation of 8-lipoxygenase metabolites does not appear to depend on the ion current since an influx of chloride ions is neither necessary nor sufficient for the formation of the lipid metabolites. In addition, the application of pertussis toxin blocked the ACh-activated release of arachidonic acid and the subsequent production of 8-lipoxygenase metabolites, yet the ACh-induced activation of the chloride conductance is not dependent on a G protein. Our results are consistent with the idea that the nicotinic ACh receptor that activates the sustained chloride conductance can, independent of the chloride ion influx, initiate lipid messenger synthesis.
authors.affiliation: Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Tieman
authors.forename: D J
authors.initials: DJ
authors.lastname: Steel
authors.forename: Y
authors.initials: Y
authors.lastname: Gor
authors.forename: J
authors.initials: J
authors.lastname: Kehoe
authors.forename: J H
authors.initials: JH
authors.lastname: Schwartz
authors.forename: S J
authors.initials: SJ
authors.lastname: Feinmark
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001048:Aplysia; D001091:Arachidonate Lipoxygenases / Q000378:metabolism*; D001095:Arachidonic Acids / Q000096:biosynthesis; D001115:Arecoline / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D018118:Chloride Channels / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D002794:Choline / Q000031:analogs & derivatives / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D020916:Conotoxins / Q000494:pharmacology; D003864:Depression, Chemical; D004789:Enzyme Activation / Q000187:drug effects; D017952:Ganglia, Invertebrate / Q000166:cytology; D018738:Hexamethonium / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D037342:Pertussis Toxin; D020239:Receptor Cross-Talk / Q000502:physiology; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
chemical_list: C107629:8-keto-5,9,11,14-eicosatetraenoic acid; D001095:Arachidonic Acids; D002038:Bungarotoxins; D018118:Chloride Channels; D002712:Chlorides; D018680:Cholinergic Antagonists; D020916:Conotoxins; D006893:Hydroxyeicosatetraenoic Acids; D009419:Nerve Tissue Proteins; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D010566:Virulence Factors, Bordetella; C087686:alpha-conotoxin ImI; C009335:subecholine; D018738:Hexamethonium; D001115:Arecoline; D019789:Tetraethylammonium; D009538:Nicotine; C047628:8-hydroxyeicosatetraenoic acid; D001285:Atropine; D001091:Arachidonate Lipoxygenases; C054192:arachidonate 8-lipoxygenase; D037342:Pertussis Toxin; D002794:Choline; D000109:Acetylcholine; D014403:Tubocurarine