title: Arachidonic acid potentiates ACh receptor currents by protein kinase C activation but not by receptor phosphorylation.
abstract: The effects of arachidonic acid on ACh-gated channel currents were examined using Torpedo nicotinic ACh receptors expressed in Xenopus oocytes. Arachidonic acid decreased ACh-evoked currents during treatment, to a greater extent in Ca(2+)-free extracellular solution. The currents were enhanced for more than 30 min after washing, reaching 150 and 170% in Ca(2+)-containing and -free extracellular solutions, respectively. The current enhancement was inhibited by the selective protein kinase C (PKC) inhibitor, GF109203X, whereas the current depression was not affected. Furthermore, arachidonic acid-evoked current depression was blocked in mutant ACh receptors with PKC phosphorylation site deletions on the alpha and delta subunits, but the long-lasting potentiation effect remained. These results indicate that arachidonic acid may decrease ACh receptor currents by a direct binding to PKC phosphorylation sites of the ACh receptors and may potentiate the currents via a novel pathway related to arachidonic acid-regulated PKC activation, but not via PKC phosphorylation of the ACh receptor itself.
authors.affiliation: Department of Physiology, Kobe University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeuchi
authors.forename: T
authors.initials: T
authors.lastname: Nishizaki
authors.forename: T
authors.initials: T
authors.lastname: Matsuoka
authors.forename: K
authors.initials: K
authors.lastname: Sumikawa
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D004789:Enzyme Activation; D015640:Ion Channel Gating / Q000187:drug effects; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014101:Torpedo; D014981:Xenopus
chemical_list: D011950:Receptors, Cholinergic; D016718:Arachidonic Acid; D011493:Protein Kinase C