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KMID : 0578320080260020181
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Molecules and Cells
2008 Volume.26 No. 2 p.181 ~ p.185
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Calcitonin Gene-related Peptide Suppresses Pacemaker Currents by Nitric Oxide/cGMP-dependent Activation of ATP-sensitive K(+) Channels in Cultured Interstitial Cells of Cajal from the Mouse Small Intestine
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Choi Seok
Park Chan-Guk
Yeum Cheol-Ho
Jeong Han-Seong
Park Jong-Seong
Park Yeong-Bong
Jun Jae-Yeoul
Kim Young-Dae
Shankar Prasad Parajuli
Kim Man-Yoo
Cha Kyoung-Hun
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Abstract
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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?C. 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 GDP?S, 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.
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KEYWORD
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ATP-sensitive K+ channels, calcitonin gene-related peptide, interstitial cells of cajal, nitric oxide, pacemaker currents, small intestine
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