Nishizaki T, Ikeuchi Y, Matsuoka T, Sumikawa K
Department of Physiology, Kobe University School of Medicine, Japan.
Neuroreport. 1997 Feb 10;8(3):597-601. doi: 10.1097/00001756-199702100-00004.
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.
油酸是一种顺式不饱和游离脂肪酸，被认为参与蛋白激酶C（PKC）激活途径。然而，其生物学作用尚未得到充分表征。我们使用非洲爪蟾卵母细胞中表达的电鳐烟碱型乙酰胆碱受体，研究了油酸对乙酰胆碱（ACh）门控通道电流的影响。油酸（10微摩尔）增强了电流，处理后20分钟达到最大值（140%），而在无钙细胞外溶液中未观察到增强。油酸对电流的增强作用不受PKC抑制剂如PKCI或GF109203X的抑制。此外，油酸增强了缺乏潜在PKC磷酸化位点的突变型ACh受体的电流。相反，这种增强作用被CaMKII抑制剂KN-62完全抑制。这些结果强烈表明，油酸通过激活钙调蛋白依赖性蛋白激酶II（CaMKII）增强ACh受体电流，独立于PKC途径。
