Long-lasting enhancement of ACh receptor currents by lysophospholipids.
Lysophosphatidylcholine (LysoPtdCho) and lysophosphatidylethanolamine (LysoPtdEtn), which are formed by phospholipase A2-catalyzed hydrolysis of phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn), respectively, are proposed to be involved in protein kinase C (PKC) activation. Their physiological significance, however, remains unclear. We examined the effects of lysoPtdCho and lysoPtdEtn on acetylcholine (ACh) receptor currents using oocytes expressing Torpedo nicotinic ACh receptors. LysoPtdCho enhanced the currents in a washing time- and dose-dependent manner (10 nM-1 microM), reaching a maximum of 191% at 20 min after treatment. The currents were enhanced to a lesser extent at higher concentrations, and instead, inhibited to 81% at 10 microM. Likewise, lysoPtdEtn also potentiated the currents to 200% at 10 microM, although its dose-dependent curve shifted to right as compared with that of lysoPtdCho. The current potentiation was blocked by a PKC inhibitor, PKC inhibitor peptide (PKCI), or removal of extracellular Ca2+. In addition, lysoPtdCho and lysoPtdEtn enhanced the currents in mutant ACh receptors lacking PKC phosphorylation sites on the alpha and delta subunits. These results suggest that lysophospholipids such as lysoPtdCho and lysoPtdEtn potentiated ACh receptor currents by Ca2+-dependent PKC activation, but that this effect did not require PKC phosphorylation of the ACh receptor.
Ikeuchi
Y
Y
Department of Physiology, Kobe University School of Medicine, Chuo-ku, Japan.
Nishizaki
T
T
Matsuoka
T
T
Sumikawa
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008246:Lysophospholipids / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D014101:Torpedo; D014981:Xenopus
D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D011978:Receptors, Nicotinic; C008301:lysophosphatidylethanolamine; D011493:Protein Kinase C; D000109:Acetylcholine