PMID- 9106730 OWN - NLM STAT- MEDLINE DCOM- 19970703 LR - 20190718 IS - 0959-4965 (Print) IS - 0959-4965 (Linking) VI - 8 IP - 3 DP - 1997 Feb 10 TI - Oleic acid enhances ACh receptor currents by activation of Ca2+/calmodulin-dependent protein kinase II. PG - 597-601 AB - Oleic acid, a cis-unsaturated free fatty acid, is proposed to be involved in the protein kinase C (PKC) activation pathway. Its biological actions, however, have not been well-characterized. We examined the effects of oleic acid on acetylcholine (ACh)-gated channel currents using Torpedo nicotinic ACh receptors expressed in Xenopus oocytes. Oleic acid (10 microM) enhanced the currents, reaching a maximum (140%) 20 min after treatment, while no enhancement was observed in Ca(2+)-free extracellular solution. The current potentiation by oleic acid was not inhibited by PKC inhibitors such as PKCI or GF109203X. Furthermore, oleic acid potentiated the currents in mutant ACh receptors lacking potential PKC phosphorylation sites. In contrast, the potentiation was fully inhibited by a CaMKII inhibitor, KN-62. These results strongly suggest that oleic acid potentiates ACh receptor currents by activation of calmodulin-dependent protein kinase II (CaMKII), independent of the PKC pathway. FAU - Nishizaki, T AU - Nishizaki T AD - Department of Physiology, Kobe University School of Medicine, Japan. FAU - Ikeuchi, Y AU - Ikeuchi Y FAU - Matsuoka, T AU - Matsuoka T FAU - Sumikawa, K AU - Sumikawa K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Neuroreport JT - Neuroreport JID - 9100935 RN - 0 (Enzyme Inhibitors) RN - 0 (Indoles) RN - 0 (Macromolecular Substances) RN - 0 (Maleimides) RN - 0 (Receptors, Nicotinic) RN - 0 (Recombinant Proteins) RN - 2UMI9U37CP (Oleic Acid) RN - 452VLY9402 (Serine) RN - 63HM46XPOW (KN 62) RN - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - L79H6N0V6C (bisindolylmaleimide I) RN - N9YNS0M02X (Acetylcholine) SB - IM MH - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives/pharmacology MH - Acetylcholine/*pharmacology MH - Animals MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2 MH - Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/*metabolism MH - Enzyme Activation MH - Enzyme Inhibitors/pharmacology MH - Female MH - Indoles/pharmacology MH - Kinetics MH - Macromolecular Substances MH - Maleimides/pharmacology MH - Mutagenesis, Site-Directed MH - Oleic Acid/*pharmacology MH - Oocytes/*physiology MH - Point Mutation MH - Protein Kinase C/antagonists & inhibitors MH - Receptors, Nicotinic/biosynthesis/drug effects/*physiology MH - Recombinant Proteins/drug effects/metabolism MH - Serine MH - Torpedo MH - Xenopus laevis EDAT- 1997/02/10 00:00 MHDA- 1997/02/10 00:01 CRDT- 1997/02/10 00:00 PHST- 1997/02/10 00:00 [pubmed] PHST- 1997/02/10 00:01 [medline] PHST- 1997/02/10 00:00 [entrez] AID - 10.1097/00001756-199702100-00004 [doi] PST - ppublish SO - Neuroreport. 1997 Feb 10;8(3):597-601. doi: 10.1097/00001756-199702100-00004.