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Free fatty acid derivative HUHS2002 potentiates α7 ACh receptor responses through indirect activation of CaMKII.
Kanno T
,
Shimizu T
,
Tanaka A
,
Nishimoto T
,
Nishizaki T
.
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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.
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