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.
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.
Choi
Seok
S
Department of Physiology, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Parajuli
Shankar Prasad
SP
Yeum
Cheol Ho
CH
Park
Chan Guk
CG
Kim
Man Yoo
MY
Kim
Young Dae
YD
Cha
Kyoung Hun
KH
Park
Young Bong
YB
Park
Jong Seong
JS
Jeong
Han Seong
HS
Jun
Jae Yeoul
JY
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
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