Regulation of pacemaker frequency in the murine gastric antrum
Regulation of pacemaker frequency in the murine gastric antrum
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DOI：
10.1113/jphysiol.2001.012765
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发表时间：
2002-01-01
影响因子：
5.5
通讯作者：
Sanders, KM
中科院分区：
文献类型：
--
作者：
Kim, TW;Beckett, EAH;Sanders, KM
前列腺素E(2)与胃性心律失常的产生有关，如心动过速。Cajal间质细胞(ICC)在胃肠道肌肉中产生电节律，因此可能是胃肌PGE(2)的靶点。我们从小鼠胃窦培养ICC，证实细胞呈Kit免疫反应，并测量了自发慢波。这些事件是由未被硝苯地平阻断的自发内向(起搏器)电流引起的。Forsklin和8-溴腺苷3‘：5’-环磷酸腺苷(8-BR-cAMP)可降低ICC起搏电流频率和胃窦肌慢波频率。Forskolin和8-BR-cAMP的作用不能被蛋白激酶A的抑制剂阻断，这表明cAMP对起搏器活动有直接影响。PGE(2)与Forsklin和8-BrcAMP对ICC的作用相似，但增加了完整肌肉的慢波频率。因此，我们研究了前列腺素EP受体激动剂的变时性作用。Butaprost和Ono-AE1-329，EP2和EP4受体激动剂，模拟Forsklin和8-BR-cAMP对ICC和完整肌肉的作用。舒前列酮(EP3和GT；EP1激动剂)、GR63799和ONO-AE-248(EP3激动剂)增加ICC起搏电流和完整肌肉慢波的频率。舒前列酮的作用不能被EP3受体拮抗剂SC-19220阻断。这些观察表明，PGE(2)在完整肌肉中的正性变时性作用是由EP3受体刺激介导的。PGE(2)在完整肌肉中的作用可能依赖于EP受体的相对表达和/或受体与PGE(2)来源的接近程度。
PGE(2) has been linked to the production of gastric arrhythmias such as tachygastria. The interstitial cells of Cajal (ICC) generate electrical rhythmicity in gastrointestinal muscles, and may therefore be a target for PGE(2) in gastric muscles. We cultured ICC from the murine gastric antrum, verified that cells were Kit immunoreactive, and measured spontaneous slow waves. These events were caused by spontaneous inward (pacemaker) currents that were not blocked by nifedipine. Forskolin and 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP) reduced the frequency of pacemaker currents in ICC and of slow waves in intact antral muscles. The effects of forskolin and 8-Br-cAMP were not blocked by inhibitors of protein kinase A, suggesting that cAMP has direct effects on pacemaker activity. PGE(2) mimicked the effects of forskolin and 8-Br-cAMP on ICC, but increased slow-wave frequency in intact muscles. Therefore, the chronotropic effects of specific prostaglandin EP receptor agonists were examined. Butaprost and ONO-AE1-329, EP2 and EP4 receptor agonists, mimicked the effects of forskolin and 8-Br-cAMP on ICC and intact muscles. Sulprostone (EP3>EP1 agonist), GR63799, and ONO-AE-248 (EP3 agonists) enhanced the frequencies of pacemaker currents in ICC and slow waves in intact muscles. The effects of sulprostone were not blocked by SC-19220, an EP3 receptor antagonist. These observations suggest that the positive chronotropic effects of PGE(2) in intact muscles are mediated by EP3 receptor stimulation. The effects of PGE(2) in intact muscles may be dependent upon the relative expression of EP receptors and/or proximity of receptors to sources of PGE(2).