Choi Seok, Parajuli Shankar Prasad, Yeum Cheol Ho, Park Chan Guk, Kim Man Yoo, Kim Young Dae, Cha Kyoung Hun, Park Young Bong, Park Jong Seong, Jeong Han Seong, Jun Jae Yeoul
Department of Physiology, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Mol Cells. 2008 Aug 31;26(2):181-5. Epub 2008 Aug 4.
The effects of calcitonin gene-related peptide (CGRP) on pacemaker currents in cultured interstitial cells of Cajal (ICC) from the mouse small intestine were investigated using the whole-cell patch clamp technique at 30 degrees . Under voltage clamping at a holding potential of -70 mV, CGRP decreased the amplitude and frequency of pacemaker currents and activated outward resting currents. These effects were blocked by intracellular GDPbetaS, a G-protein inhibitor and glibenclamide, a specific ATP-sensitive K(+) channels blocker. During current clamping, CGRP hyperpolarized the membrane and this effect was antagonized by glibenclamide. Pretreatment with SQ-22536 (an adenylate cyclase inhibitor) or naproxen (a cyclooxygenase inhibitor) did not block the CGRP-induced effects, whereas pretreatment with ODQ (a guanylate cyclase inhibitor) or L-NAME (an inhibitor of nitric oxide synthase) did. In conclusion, CGRP inhibits pacemaker currents in ICC by generating nitric oxide via G-protein activation and so activating ATP-sensitive K(+) channels. Nitric oxide- and guanylate cyclase- dependent pathways are involved in these effects.
在30摄氏度下，使用全细胞膜片钳技术研究了降钙素基因相关肽（CGRP）对从小鼠小肠分离培养的 Cajal 间质细胞（ICC）起搏电流的影响。在 -70 mV 的钳制电位下进行电压钳制时，CGRP 降低了起搏电流的幅度和频率，并激活了外向静息电流。这些效应被细胞内 G 蛋白抑制剂 GDPβS 和特异性 ATP 敏感性钾（K(+)）通道阻滞剂格列本脲所阻断。在电流钳制期间，CGRP 使细胞膜超极化，而这种效应被格列本脲所拮抗。用 SQ - 22536（一种腺苷酸环化酶抑制剂）或萘普生（一种环氧化酶抑制剂）预处理并未阻断 CGRP 诱导的效应，而用 ODQ（一种鸟苷酸环化酶抑制剂）或 L - NAME（一种一氧化氮合酶抑制剂）预处理则可阻断。总之，CGRP 通过 G 蛋白激活产生一氧化氮，进而激活 ATP 敏感性钾通道，从而抑制 ICC 中的起搏电流。一氧化氮和鸟苷酸环化酶依赖性途径参与了这些效应。
