Novel PPARγ agonists GI 262570, GW 7845, GW 1929, and pioglitazone decrease calcium channel function and myogenic tone in rat mesenteric arteries
Novel PPARγ agonists GI 262570, GW 7845, GW 1929, and pioglitazone decrease calcium channel function and myogenic tone in rat mesenteric arteries
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DOI：
10.1159/000081070
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发表时间：
2005-01-01
期刊：
影响因子：
3.1
通讯作者：
Nelson, MT
中科院分区：
文献类型：
--
作者：
Heppner, TJ;Bonev, AD;Nelson, MT
研究了Glaxo-Smith-Kline（GSK）沿着吡格列酮和尼索地平开发的新型非噻唑烷二酮酪氨酸衍生的过氧化物酶体增殖物激活受体γ激动剂GI 262570、GW 7845、GW 1929对新鲜分离的肠系膜动脉平滑肌细胞L型电压依赖性钙通道（VDCC）电流的影响，对离体肠系膜动脉直径的影响。通过VDCC使用Ba 2+（10 mmol/l）作为电荷载体，GI 262570、GW 7845、GW 1929和吡格列酮的半抑制常数（IC 50）分别为2.0 +/- 0.5、3.0 +/- 0.5、5.0 +/- 0.7和10.0 +/- 0.8 mumol/l。对于动脉直径测量，GI 262570、GW 7845、GW 1929和吡格列酮的IC 50值分别为2.4、4.1、6.3和13.9 mumol/l。每种GSK化合物和吡格列酮均可有效抑制VDCC和舒张加压动脉，表明阻力动脉的血管舒张可通过抑制钙通过VDCC进入来解释。版权所有（C）2005 S. Karger AG，巴塞尔。
Novel non-thiazolidinedione, tyrosine-derived peroxisome proliferator-activated receptor gamma agonists, GI 262570, GW 7845, GW 1929, developed by Glaxo-Smith-Kline (GSK) along with pioglitazone and nisoldipine, were studied on currents through L-type voltage-dependent calcium channels (VDCC) in freshly isolated smooth muscle cells from mesenteric arteries, and on the diameter of pressurized mesenteric arteries in vitro. Using Ba2+ (10 mmol/l) as the charge carrier through VDCC, the half-inhibition constants (IC50) for GI 262570, GW 7845, GW 1929, and pioglitazone were 2.0 +/- 0.5, 3.0 +/- 0.5, 5.0 +/- 0.7, and 10.0 +/- 0.8 mumol/l, respectively. For arterial diameter measurements the IC50 values for GI 262570, GW 7845, GW 1929, and pioglitazone were 2.4, 4.1, 6.3, and 13.9 mumol/l, respectively. Each GSK compound and pioglitazone was effective at inhibiting VDCC and relaxing pressurized arteries, suggesting that the vasodilation of resistance arteries could be explained by the inhibition of calcium entry through VDCC. Copyright (C) 2005 S. Karger AG, Basel.