Substance P induces inward current and regulates pacemaker currents through tachykinin NK1 receptor in cultured interstitial cells of Cajal of murine small intestine
Substance P induces inward current and regulates pacemaker currents through tachykinin NK1 receptor in cultured interstitial cells of Cajal of murine small intestine
复制标题
DOI：
10.1016/j.ejphar.2004.05.022
复制
发表时间：
2004-07-08
影响因子：
5
通讯作者：
Kim, KW
中科院分区：
文献类型：
--
作者：
Jun, JY;Choi, S;Kim, KW
我们使用全细胞膜片钳技术在 30 摄氏度下研究了 P 物质是否调节培养的小鼠小肠 Cajal 间质细胞中产生的起搏器电流。 Cajal 间质细胞在 -70 mV 的保持电位下产生自发内向电流（起搏器电流）。河豚毒素、硝苯地平、四乙铵、4-氨基吡啶或格列本脲不会改变起搏器电流的频率和幅度。然而，二价阳离子（Ni2+、Mn2+、Cd2+ 和 Co2+）、非选择性阳离子通道阻滞剂（钆和氟芬那酸）以及外部 Na+ 从正常减少至 1 mM 会抑制起搏器电流，表明非选择性阳离子通道参与其生成。 P物质在电流7,9钳模式下使膜电位去极化，并在电压钳模式下产生频率和幅度降低的强直内向起搏器电流。 [D-Arg(1), D-Trp(7,9) Leu(11)] P 物质是一种速激肽 NK1 受体拮抗剂，可阻断这些 P 物质诱导的反应。此外，[Sar(9), Met(O-2)(11)] P 物质（一种特定的速激肽 NK1 受体激动剂）使膜去极化，并且产生类似于 P 物质的强直内向电流。P 物质在外部无 Ca2+ 溶液中或在白屈菜红碱（一种蛋白激酶 C 抑制剂）存在下继续产生强直内向电流。然而，P 物质诱导的强直内向电流被毒胡萝卜素（内质网中的一种 Ca2+-ATP 酶抑制剂）或外部 1 mM Na+ 溶液阻断。我们的结果表明，P 物质可能通过刺激速激肽 NK1 受体刺激诱导的细胞内 Ca2+ 释放，激活非选择性阳离子通道，作用于 Cajal 间质细胞，从而调节肠道蠕动。 (C) 2004 Elsevier B.V. 保留所有权利。
We investigated whether substance P modulates pacemaker currents generated in cultured interstitial cells of Cajal of murine small intestine using whole cell patch-clamp techniques at 30 degreesC. Interstitial cells of Cajal generated spontaneous inward currents (pacemaker currents) at a holding potential of -70 mV Tetrodotoxin, nifedipine, tetraethylammonium, 4-aminopyridine, or glibenclamide did not change the frequency and amplitude of pacemaker currents. However, divalent cations (Ni2+, Mn2+, Cd2+, and Co2+), nonselective cationic channel blockers (gadolinium and flufenamic acid), and a reduction of external Na+ from normal to 1 mM inhibited pacemaker currents indicating that nonselective cation channels are involved in their generation. Substance P depolarized the membrane potential in current 7,9 clamp mode and produced tonic inward pacemaker currents with reduced frequency and amplitude in voltage clamp mode. [D-Arg(1), D-Trp(7,9) Leu(11)] substance P, a tachykinin NK1 receptor antagonist, blocked these substance P-induced responses. Furthermore, [Sar(9), Met(O-2)(11)] substance P, a specific tachykinin NK1 receptor agonist, depolarized the membrane and tonic inward currents mimicked those of substance P. Substance P continued to produce tonic inward currents in external Ca2+-free solution or in the presence of chelerythrine, a protein kinase C inhibitor. However, substance P-induced tonic inward currents were blocked by thapsigargin, a Ca2+-ATPase inhibitor in the endoplasmic reticulum or by an external 1 mM Na+ solution. Our results demonstrate that substance P may modulate intestinal motility by acting on the interstitial cells of Cajal by activating nonselective cation channels via the release of intracellular Ca2+ induced by tachykinin NK1 receptor stimulation. (C) 2004 Elsevier B.V. All rights reserved.