Basal cGMP regulates the resting pacemaker potential frequency of cultured mouse colonic interstitial cells of Cajal

Pawan Kumar Shahi, Seok Choi, Yu Jin Jeong, Chan Guk Park, Insuk So, Jae Yeoul Jun

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

Cyclic guanosine 3′,5′-monophosphate (cGMP) inhibited the generation of pacemaker activity in interstitial cells of Cajal (ICCs) from the small intestine. However, cGMP role on pacemaker activity in colonic ICCs has not been reported yet. Thus, we investigated the role of cGMP in pacemaker activity regulation by colonic ICCs. We performed a whole-cell patch-clamp and Ca 2+ imaging in cultured ICCs from mouse colon. 1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) increased the pacemaker potential frequency, whereas zaprinast (an inhibitor of phosphodiesterase) and cell-permeable 8-bromo-cGMP decreased the pacemaker potential frequency. KT-5823 (an inhibitor of protein kinase G [PKG]) did not affect the pacemaker potential. L-N G -nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide [NO] synthase) increased the pacemaker potential frequency, whereas (±)-S-nitroso-N-acetylpenicillamine (SNAP, a NO donor) decreased the pacemaker potential frequency. Glibenclamide (an ATP-sensitive K + channel blocker) did not block the effects of cell-permeable 8-bromo-cGMP and SNAP. Recordings of spontaneous intracellular Ca 2+ ([Ca 2+ ] i ) oscillations revealed that ODQ and L-NAME increased [Ca 2+ ] i oscillations. In contrast, zaprinast, 8-bromo cGMP, and SNAP decreased the [Ca 2+ ] i oscillations. Basal cGMP levels regulate the resting pacemaker potential frequency by the alteration on Ca 2+ release via a PKG-independent pathway. Additionally, the endogenous release of NO seems to be responsible maintaining basal cGMP levels in colonic ICCs.

Original languageEnglish
Pages (from-to)641-648
Number of pages8
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume387
Issue number7
DOIs
StatePublished - 1 Jan 2014

Fingerprint

Interstitial Cells of Cajal
Guanosine Monophosphate
Membrane Potentials
NG-Nitroarginine Methyl Ester
Cyclic GMP-Dependent Protein Kinases
S-Nitroso-N-Acetylpenicillamine
Phosphodiesterase Inhibitors
Nitric Oxide Donors
Glyburide
Guanylate Cyclase
Nitric Oxide Synthase
Small Intestine
Cultured Cells
Nitric Oxide
Colon
Adenosine Triphosphate

Keywords

  • Colon
  • Gastrointestinal motility
  • Interstitial cells of Cajal
  • Nitric oxide
  • cGMP

Cite this

Shahi, Pawan Kumar ; Choi, Seok ; Jeong, Yu Jin ; Park, Chan Guk ; So, Insuk ; Jun, Jae Yeoul. / Basal cGMP regulates the resting pacemaker potential frequency of cultured mouse colonic interstitial cells of Cajal. In: Naunyn-Schmiedeberg's Archives of Pharmacology. 2014 ; Vol. 387, No. 7. pp. 641-648.
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abstract = "Cyclic guanosine 3′,5′-monophosphate (cGMP) inhibited the generation of pacemaker activity in interstitial cells of Cajal (ICCs) from the small intestine. However, cGMP role on pacemaker activity in colonic ICCs has not been reported yet. Thus, we investigated the role of cGMP in pacemaker activity regulation by colonic ICCs. We performed a whole-cell patch-clamp and Ca 2+ imaging in cultured ICCs from mouse colon. 1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) increased the pacemaker potential frequency, whereas zaprinast (an inhibitor of phosphodiesterase) and cell-permeable 8-bromo-cGMP decreased the pacemaker potential frequency. KT-5823 (an inhibitor of protein kinase G [PKG]) did not affect the pacemaker potential. L-N G -nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide [NO] synthase) increased the pacemaker potential frequency, whereas (±)-S-nitroso-N-acetylpenicillamine (SNAP, a NO donor) decreased the pacemaker potential frequency. Glibenclamide (an ATP-sensitive K + channel blocker) did not block the effects of cell-permeable 8-bromo-cGMP and SNAP. Recordings of spontaneous intracellular Ca 2+ ([Ca 2+ ] i ) oscillations revealed that ODQ and L-NAME increased [Ca 2+ ] i oscillations. In contrast, zaprinast, 8-bromo cGMP, and SNAP decreased the [Ca 2+ ] i oscillations. Basal cGMP levels regulate the resting pacemaker potential frequency by the alteration on Ca 2+ release via a PKG-independent pathway. Additionally, the endogenous release of NO seems to be responsible maintaining basal cGMP levels in colonic ICCs.",
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Basal cGMP regulates the resting pacemaker potential frequency of cultured mouse colonic interstitial cells of Cajal. / Shahi, Pawan Kumar; Choi, Seok; Jeong, Yu Jin; Park, Chan Guk; So, Insuk; Jun, Jae Yeoul.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 387, No. 7, 01.01.2014, p. 641-648.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Basal cGMP regulates the resting pacemaker potential frequency of cultured mouse colonic interstitial cells of Cajal

AU - Shahi, Pawan Kumar

AU - Choi, Seok

AU - Jeong, Yu Jin

AU - Park, Chan Guk

AU - So, Insuk

AU - Jun, Jae Yeoul

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AB - Cyclic guanosine 3′,5′-monophosphate (cGMP) inhibited the generation of pacemaker activity in interstitial cells of Cajal (ICCs) from the small intestine. However, cGMP role on pacemaker activity in colonic ICCs has not been reported yet. Thus, we investigated the role of cGMP in pacemaker activity regulation by colonic ICCs. We performed a whole-cell patch-clamp and Ca 2+ imaging in cultured ICCs from mouse colon. 1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) increased the pacemaker potential frequency, whereas zaprinast (an inhibitor of phosphodiesterase) and cell-permeable 8-bromo-cGMP decreased the pacemaker potential frequency. KT-5823 (an inhibitor of protein kinase G [PKG]) did not affect the pacemaker potential. L-N G -nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide [NO] synthase) increased the pacemaker potential frequency, whereas (±)-S-nitroso-N-acetylpenicillamine (SNAP, a NO donor) decreased the pacemaker potential frequency. Glibenclamide (an ATP-sensitive K + channel blocker) did not block the effects of cell-permeable 8-bromo-cGMP and SNAP. Recordings of spontaneous intracellular Ca 2+ ([Ca 2+ ] i ) oscillations revealed that ODQ and L-NAME increased [Ca 2+ ] i oscillations. In contrast, zaprinast, 8-bromo cGMP, and SNAP decreased the [Ca 2+ ] i oscillations. Basal cGMP levels regulate the resting pacemaker potential frequency by the alteration on Ca 2+ release via a PKG-independent pathway. Additionally, the endogenous release of NO seems to be responsible maintaining basal cGMP levels in colonic ICCs.

KW - Colon

KW - Gastrointestinal motility

KW - Interstitial cells of Cajal

KW - Nitric oxide

KW - cGMP

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U2 - 10.1007/s00210-014-0976-2

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