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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  

Choi, Seok (Department of Physiology, College of Medicine, Chosun University)
Parajuli, Shankar Prasad (Department of Physiology, College of Medicine, Chosun University)
Yeum, Cheol Ho (Department of Physiology, College of Medicine, Chosun University)
Park, Chan Guk (Department of Internal Medicine, College of Medicine, Chosun University)
Kim, Man Yoo (Department of Internal Medicine, College of Medicine, Chosun University)
Kim, Young Dae (Department of Internal Medicine, College of Medicine, Chosun University)
Cha, Kyoung Hun (Department of Pediatrics, College of Medicine, Chosun University)
Park, Young Bong (Department of Pediatrics, College of Medicine, Chosun University)
Park, Jong Seong (Department of Physiology Chonnam National University Medical School)
Jeong, Han Seong (Department of Physiology Chonnam National University Medical School)
Jun, Jae Yeoul (Department of Physiology, College of Medicine, Chosun University)
Publication Information
Molecules and Cells / v.26, no.2, 2008 , pp. 181-185 More about this Journal
Abstract
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 $30^{\circ}C$. 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 $GDP{\beta}S$, 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.
Keywords
ATP-sensitive $K^+$ channels; calcitonin gene-related peptide; interstitial cells of cajal; nitric oxide; pacemaker currents; small intestine;
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Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 3  (Related Records In Web of Science)
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