title: 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.
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 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.
authors.affiliation: Department of Physiology, College of Medicine, Chosun University, Gwangju 501-759, Korea.
authors.forename: Seok
authors.initials: S
authors.lastname: Choi
authors.forename: Shankar Prasad
authors.initials: SP
authors.lastname: Parajuli
authors.forename: Cheol Ho
authors.initials: CH
authors.lastname: Yeum
authors.forename: Chan Guk
authors.initials: CG
authors.lastname: Park
authors.forename: Man Yoo
authors.initials: MY
authors.lastname: Kim
authors.forename: Young Dae
authors.initials: YD
authors.lastname: Kim
authors.forename: Kyoung Hun
authors.initials: KH
authors.lastname: Cha
authors.forename: Young Bong
authors.initials: YB
authors.lastname: Park
authors.forename: Jong Seong
authors.initials: JS
authors.lastname: Park
authors.forename: Han Seong
authors.initials: HS
authors.lastname: Jeong
authors.forename: Jae Yeoul
authors.initials: JY
authors.lastname: Jun
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000494:pharmacology*; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007421:Intestine, Small / Q000166:cytology / Q000502:physiology*; D054086:KATP Channels / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D054086:KATP Channels; D010069:Oxadiazoles; D011810:Quinoxalines; C017759:9-(tetrahydro-2-furyl)-adenine; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D000225:Adenine; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester