title: Free fatty acid derivative HUHS2002 potentiates α7 ACh receptor responses through indirect activation of CaMKII.
abstract: The present study examined the effect of 4-[4-(Z)-hept-1-enyl-phenoxy] butyric acid (HUHS2002), a free fatty acid derivative, on α7 acetylcholine (ACh) receptor responses. HUHS2002 potentiated whole-cell membrane currents through α7 ACh receptors expressed in Xenopus oocytes in a concentration (1-100 nM)-dependent manner, reaching about 140 % of the original amplitude at 100 nM 50 min after a 10-min treatment. The HUHS2002 effect was prevented by KN-93, an inhibitor of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), while it was not affected by GF109203X, an inhibitor of protein kinase C (PKC), or H-89, an inhibitor of protein kinase A (PKA). In the in situ CaMKII assay using cultured rat hippocampal neurons, HUHS2002 activated CaMKII and the activation was abolished by KN-93. In the cell-free assay of protein phosphatase 1 (PP1), HUHS2002 partially inhibited PP1 activity. Taken together, these results indicate that HUHS2002 potentiates α7 ACh receptor responses by indirectly activating CaMKII, possibly via inhibition of PP1.
authors: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
authors: Takeshi
authors: T
authors: Kanno
authors: Tadashi
authors: T
authors: Shimizu
authors: Akito
authors: A
authors: Tanaka
authors: Takaaki
authors: T
authors: Nishimoto
authors: Tomoyuki
authors: T
authors: Nishizaki
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology; D002087:Butyrates / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects*; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014981:Xenopus / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C577567:4-(4-hept-1-enylphenoxy)butyric acid; D002087:Butyrates; C579165:Chrna7 protein, rat; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D054645:Protein Phosphatase 1