Lu Hong-Li, Wang Zuo-Yu, Huang Xu, Han Yan-Fei, Wu Yi-Song, Guo Xin, Kim Yong-Chul, Xu Wen-Xie
Department of Physiology, Shanghai Jiaotong University School of Medicine, 800 Dongchuan Road, 328# Wenxuan Medical Building, Shanghai, 200240, China.
Regul Pept. 2011 Apr 11;167(2-3):170-6. doi: 10.1016/j.regpep.2011.01.004. Epub 2011 Jan 21.
In the present study, we investigated the effect of Ang II on gastric smooth muscle motility and its mechanism using intracellular recording and whole-cell patch clamp techniques. Ang II dose-dependently increased the tonic contraction and the frequency of spontaneous contraction in the gastric antral circular smooth muscles of guinea pig. ZD7155, an Ang II type 1 receptor (AT(1)R) blocker, completely blocked the effect of Ang II on the spontaneous contraction of gastric smooth muscle. In contrast, TTX, a sodium channel blocker, failed to block the effect. Furthermore, nicardipine, a voltage-gated Ca(2+)-channel antagonist, did not block the effect of Ang II on the tonic contraction of gastric smooth muscle, but external free-calcium almost completely blocked this effect. Both ryanodine, an inhibitor of calcium-induced Ca(2+) release (CICR) from ryanodine-sensitive calcium stores, and thapsigargin, which depletes calcium in calcium stores, almost completely blocked the effect of Ang II on tonic contraction. However, 2-APB, an inositol trisphosphate (IP(3)) receptor blocker, significantly, but not completely, blocked the Ang II effect on tonic contraction. We also determined that Ang II depolarized membrane potential and increased slow wave frequency in a dose-dependent manner. It also inhibited delayed rectifying potassium currents in a dose-dependent manner, but did not affect L-type calcium currents or calcium-activated potassium currents. These results suggest that Ang II plays an excitatory regulation in gastric motility via AT(1)R-IP(3) and the CICR signaling pathway. The Ang II-induced inhibition of delayed rectifying potassium currents that depolarize membrane potential is also involved in the potentiation of tonic contraction and the frequency of spontaneous contraction in the gastric smooth muscle of guinea pig.
在本研究中，我们使用细胞内记录和全细胞膜片钳技术研究了血管紧张素II（Ang II）对胃平滑肌运动的影响及其机制。Ang II剂量依赖性地增加了豚鼠胃窦环行平滑肌的张力性收缩和自发收缩频率。血管紧张素II 1型受体（AT(1)R）阻滞剂ZD7155完全阻断了Ang II对胃平滑肌自发收缩的作用。相比之下，钠通道阻滞剂河豚毒素（TTX）未能阻断该作用。此外，电压门控钙通道拮抗剂尼卡地平未阻断Ang II对胃平滑肌张力性收缩的作用，但细胞外游离钙几乎完全阻断了该作用。钙诱导钙释放（CICR）的抑制剂ryanodine和耗尽钙库中钙的毒胡萝卜素几乎完全阻断了Ang II对张力性收缩的作用。然而，肌醇三磷酸（IP(3)）受体阻滞剂2-APB显著但未完全阻断Ang II对张力性收缩的作用。我们还确定Ang II以剂量依赖性方式使膜电位去极化并增加慢波频率。它还以剂量依赖性方式抑制延迟整流钾电流，但不影响L型钙电流或钙激活钾电流。这些结果表明，Ang II通过AT(1)R-IP(3)和CICR信号通路对胃运动起兴奋性调节作用。Ang II诱导的延迟整流钾电流抑制使膜电位去极化，这也参与了豚鼠胃平滑肌张力性收缩和自发收缩频率的增强。
