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최석,Shankar Prasad Parajuli,염철호,박찬국,김만유,김영대,차경훈,박영봉,박종성,정한성,전제열 한국분자세포생물학회 2008 Molecules and cells Vol.26 No.2
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 30C. 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 GDPS, 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.