Noradrenaline inhibits pacemaker currents through stimulation of β 1 -adrenoceptors in cultured interstitial cells of Cajal from murine small intestine

Jae Yeoul Jun, Seok Choi, Cheol Ho Yeum, In Youb Chang, Chan Kuk Park, Man Yoo Kim, In Deok Kong, Insuk So, Ki Whan Kim, Ho Jin You

Research output: Contribution to journalArticleResearchpeer-review

28 Citations (Scopus)

Abstract

1 Interstitial cells of Cajal (ICCs) are pacemaker cells that activate the periodic spontaneous inward currents (pacemaker currents) responsible for the production of slow waves in gastrointestinal smooth muscle. The effects of noradrenaline on the pacemaker currents in cultured ICCs from murine small intestine were investigated by using whole-cell patch-clamp techniques at 30°C. 2 Under current clamping, ICCs had a mean resting membrane potential of -58±5mV and produced electrical slow waves. Under voltage clamping, ICCs produced pacemaker currents with a mean amplitude of -410±57 pA and a mean frequency of 16±2 cycles min -1 . 3 Under voltage clamping, noradrenaline inhibited the amplitude and frequency of pacemaker currents and increased resting currents in the outward direction in a dose-dependent manner. These effects were reduced by intracellular GDPβS. 4 Noradrenaline-induced effects were blocked by propranolol (β- adrenoceptor antagonist). However, neither prazosin (α 1 - adrenoceptor antagonist) nor yohimbine (α 2 -adrenoceptor antagonist) blocked the noradrenaline-induced effects. Phenylephrine (α 1 -adrenoceptor agonist) had no effect on the pacemaker currents, whereas isoprenaline (β-adrenoceptor agonist) mimicked the effect of noradrenaline. Atenolol (β 1 -adrenoceptor antagonist) blocked the noradrenaline-induced effects, but butoxamine (β 2 - adrenoceptor antagonist) did not. In addition, BRL37344 (β 3 - adrenoceptor agonist) had no effect on pacemaker currents. 5 9-(Tetrahydro-2-furanyl)-9H-purine-6-amine (SQ-22536; adenylate cyclase inhibitor) and a myristoylated protein kinase A inhibitor did not inhibit the noradrenaline-induced effects and 8-bromo-cAMP had no effects on pacemaker currents. 8-Bromo-cGMP and SNAP inhibited pacemaker currents and these effects of SNAP were blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a guanylate cyclase inhibitor). However, ODQ did not block the noradrenaline-induced effects. 6 Neither tetraethylammonium (a voltage-dependent K + channel blocker), apamin (a Ca 2+ -dependent K + channel blocker) nor glibenclamide (an ATP-sensitive K + channel blocker) blocked the noradrenaline-induced effects. 7 The results suggest that noradrenaline-induced stimulation of β 1 -adrenoceptors in the ICCs inhibits pacemaker currents, and that this is mediated by the activation of G-protein. Neither adenylate cyclase, guanylate cyclase nor a K + channel-dependent pathway are involved in this effect of noradrenaline.

Original languageEnglish
Pages (from-to)670-677
Number of pages8
JournalBritish Journal of Pharmacology
Volume141
Issue number4
DOIs
StatePublished - 1 Feb 2004

Fingerprint

Interstitial Cells of Cajal
Adrenergic Receptors
Small Intestine
Cultured Cells
Norepinephrine
Constriction
Guanylate Cyclase
Butoxamine
Apamin
8-Bromo Cyclic Adenosine Monophosphate
Tetraethylammonium
Atenolol
Yohimbine
Glyburide
Prazosin
Phenylephrine
Patch-Clamp Techniques
Protein Kinase Inhibitors
Cyclic AMP-Dependent Protein Kinases
Isoproterenol

Keywords

  • Interstitial cells of Cajal
  • Noradrenaline
  • Pacemaker currents
  • Slow waves
  • β -adrenoceptor

Cite this

Jun, Jae Yeoul ; Choi, Seok ; Yeum, Cheol Ho ; Chang, In Youb ; Park, Chan Kuk ; Kim, Man Yoo ; Kong, In Deok ; So, Insuk ; Kim, Ki Whan ; You, Ho Jin. / Noradrenaline inhibits pacemaker currents through stimulation of β 1 -adrenoceptors in cultured interstitial cells of Cajal from murine small intestine In: British Journal of Pharmacology. 2004 ; Vol. 141, No. 4. pp. 670-677.
@article{b108bcc7152a4301bcb2315ef8bac66a,
title = "Noradrenaline inhibits pacemaker currents through stimulation of β 1 -adrenoceptors in cultured interstitial cells of Cajal from murine small intestine",
abstract = "1 Interstitial cells of Cajal (ICCs) are pacemaker cells that activate the periodic spontaneous inward currents (pacemaker currents) responsible for the production of slow waves in gastrointestinal smooth muscle. The effects of noradrenaline on the pacemaker currents in cultured ICCs from murine small intestine were investigated by using whole-cell patch-clamp techniques at 30°C. 2 Under current clamping, ICCs had a mean resting membrane potential of -58±5mV and produced electrical slow waves. Under voltage clamping, ICCs produced pacemaker currents with a mean amplitude of -410±57 pA and a mean frequency of 16±2 cycles min -1 . 3 Under voltage clamping, noradrenaline inhibited the amplitude and frequency of pacemaker currents and increased resting currents in the outward direction in a dose-dependent manner. These effects were reduced by intracellular GDPβS. 4 Noradrenaline-induced effects were blocked by propranolol (β- adrenoceptor antagonist). However, neither prazosin (α 1 - adrenoceptor antagonist) nor yohimbine (α 2 -adrenoceptor antagonist) blocked the noradrenaline-induced effects. Phenylephrine (α 1 -adrenoceptor agonist) had no effect on the pacemaker currents, whereas isoprenaline (β-adrenoceptor agonist) mimicked the effect of noradrenaline. Atenolol (β 1 -adrenoceptor antagonist) blocked the noradrenaline-induced effects, but butoxamine (β 2 - adrenoceptor antagonist) did not. In addition, BRL37344 (β 3 - adrenoceptor agonist) had no effect on pacemaker currents. 5 9-(Tetrahydro-2-furanyl)-9H-purine-6-amine (SQ-22536; adenylate cyclase inhibitor) and a myristoylated protein kinase A inhibitor did not inhibit the noradrenaline-induced effects and 8-bromo-cAMP had no effects on pacemaker currents. 8-Bromo-cGMP and SNAP inhibited pacemaker currents and these effects of SNAP were blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a guanylate cyclase inhibitor). However, ODQ did not block the noradrenaline-induced effects. 6 Neither tetraethylammonium (a voltage-dependent K + channel blocker), apamin (a Ca 2+ -dependent K + channel blocker) nor glibenclamide (an ATP-sensitive K + channel blocker) blocked the noradrenaline-induced effects. 7 The results suggest that noradrenaline-induced stimulation of β 1 -adrenoceptors in the ICCs inhibits pacemaker currents, and that this is mediated by the activation of G-protein. Neither adenylate cyclase, guanylate cyclase nor a K + channel-dependent pathway are involved in this effect of noradrenaline.",
keywords = "Interstitial cells of Cajal, Noradrenaline, Pacemaker currents, Slow waves, β -adrenoceptor",
author = "Jun, {Jae Yeoul} and Seok Choi and Yeum, {Cheol Ho} and Chang, {In Youb} and Park, {Chan Kuk} and Kim, {Man Yoo} and Kong, {In Deok} and Insuk So and Kim, {Ki Whan} and You, {Ho Jin}",
year = "2004",
month = "2",
day = "1",
doi = "10.1038/sj.bjp.0705665",
language = "English",
volume = "141",
pages = "670--677",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "4",

}

Noradrenaline inhibits pacemaker currents through stimulation of β 1 -adrenoceptors in cultured interstitial cells of Cajal from murine small intestine . / Jun, Jae Yeoul; Choi, Seok; Yeum, Cheol Ho; Chang, In Youb; Park, Chan Kuk; Kim, Man Yoo; Kong, In Deok; So, Insuk; Kim, Ki Whan; You, Ho Jin.

In: British Journal of Pharmacology, Vol. 141, No. 4, 01.02.2004, p. 670-677.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Noradrenaline inhibits pacemaker currents through stimulation of β 1 -adrenoceptors in cultured interstitial cells of Cajal from murine small intestine

AU - Jun, Jae Yeoul

AU - Choi, Seok

AU - Yeum, Cheol Ho

AU - Chang, In Youb

AU - Park, Chan Kuk

AU - Kim, Man Yoo

AU - Kong, In Deok

AU - So, Insuk

AU - Kim, Ki Whan

AU - You, Ho Jin

PY - 2004/2/1

Y1 - 2004/2/1

N2 - 1 Interstitial cells of Cajal (ICCs) are pacemaker cells that activate the periodic spontaneous inward currents (pacemaker currents) responsible for the production of slow waves in gastrointestinal smooth muscle. The effects of noradrenaline on the pacemaker currents in cultured ICCs from murine small intestine were investigated by using whole-cell patch-clamp techniques at 30°C. 2 Under current clamping, ICCs had a mean resting membrane potential of -58±5mV and produced electrical slow waves. Under voltage clamping, ICCs produced pacemaker currents with a mean amplitude of -410±57 pA and a mean frequency of 16±2 cycles min -1 . 3 Under voltage clamping, noradrenaline inhibited the amplitude and frequency of pacemaker currents and increased resting currents in the outward direction in a dose-dependent manner. These effects were reduced by intracellular GDPβS. 4 Noradrenaline-induced effects were blocked by propranolol (β- adrenoceptor antagonist). However, neither prazosin (α 1 - adrenoceptor antagonist) nor yohimbine (α 2 -adrenoceptor antagonist) blocked the noradrenaline-induced effects. Phenylephrine (α 1 -adrenoceptor agonist) had no effect on the pacemaker currents, whereas isoprenaline (β-adrenoceptor agonist) mimicked the effect of noradrenaline. Atenolol (β 1 -adrenoceptor antagonist) blocked the noradrenaline-induced effects, but butoxamine (β 2 - adrenoceptor antagonist) did not. In addition, BRL37344 (β 3 - adrenoceptor agonist) had no effect on pacemaker currents. 5 9-(Tetrahydro-2-furanyl)-9H-purine-6-amine (SQ-22536; adenylate cyclase inhibitor) and a myristoylated protein kinase A inhibitor did not inhibit the noradrenaline-induced effects and 8-bromo-cAMP had no effects on pacemaker currents. 8-Bromo-cGMP and SNAP inhibited pacemaker currents and these effects of SNAP were blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a guanylate cyclase inhibitor). However, ODQ did not block the noradrenaline-induced effects. 6 Neither tetraethylammonium (a voltage-dependent K + channel blocker), apamin (a Ca 2+ -dependent K + channel blocker) nor glibenclamide (an ATP-sensitive K + channel blocker) blocked the noradrenaline-induced effects. 7 The results suggest that noradrenaline-induced stimulation of β 1 -adrenoceptors in the ICCs inhibits pacemaker currents, and that this is mediated by the activation of G-protein. Neither adenylate cyclase, guanylate cyclase nor a K + channel-dependent pathway are involved in this effect of noradrenaline.

AB - 1 Interstitial cells of Cajal (ICCs) are pacemaker cells that activate the periodic spontaneous inward currents (pacemaker currents) responsible for the production of slow waves in gastrointestinal smooth muscle. The effects of noradrenaline on the pacemaker currents in cultured ICCs from murine small intestine were investigated by using whole-cell patch-clamp techniques at 30°C. 2 Under current clamping, ICCs had a mean resting membrane potential of -58±5mV and produced electrical slow waves. Under voltage clamping, ICCs produced pacemaker currents with a mean amplitude of -410±57 pA and a mean frequency of 16±2 cycles min -1 . 3 Under voltage clamping, noradrenaline inhibited the amplitude and frequency of pacemaker currents and increased resting currents in the outward direction in a dose-dependent manner. These effects were reduced by intracellular GDPβS. 4 Noradrenaline-induced effects were blocked by propranolol (β- adrenoceptor antagonist). However, neither prazosin (α 1 - adrenoceptor antagonist) nor yohimbine (α 2 -adrenoceptor antagonist) blocked the noradrenaline-induced effects. Phenylephrine (α 1 -adrenoceptor agonist) had no effect on the pacemaker currents, whereas isoprenaline (β-adrenoceptor agonist) mimicked the effect of noradrenaline. Atenolol (β 1 -adrenoceptor antagonist) blocked the noradrenaline-induced effects, but butoxamine (β 2 - adrenoceptor antagonist) did not. In addition, BRL37344 (β 3 - adrenoceptor agonist) had no effect on pacemaker currents. 5 9-(Tetrahydro-2-furanyl)-9H-purine-6-amine (SQ-22536; adenylate cyclase inhibitor) and a myristoylated protein kinase A inhibitor did not inhibit the noradrenaline-induced effects and 8-bromo-cAMP had no effects on pacemaker currents. 8-Bromo-cGMP and SNAP inhibited pacemaker currents and these effects of SNAP were blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a guanylate cyclase inhibitor). However, ODQ did not block the noradrenaline-induced effects. 6 Neither tetraethylammonium (a voltage-dependent K + channel blocker), apamin (a Ca 2+ -dependent K + channel blocker) nor glibenclamide (an ATP-sensitive K + channel blocker) blocked the noradrenaline-induced effects. 7 The results suggest that noradrenaline-induced stimulation of β 1 -adrenoceptors in the ICCs inhibits pacemaker currents, and that this is mediated by the activation of G-protein. Neither adenylate cyclase, guanylate cyclase nor a K + channel-dependent pathway are involved in this effect of noradrenaline.

KW - Interstitial cells of Cajal

KW - Noradrenaline

KW - Pacemaker currents

KW - Slow waves

KW - β -adrenoceptor

UR - http://www.scopus.com/inward/record.url?scp=11144356099&partnerID=8YFLogxK

U2 - 10.1038/sj.bjp.0705665

DO - 10.1038/sj.bjp.0705665

M3 - Article

VL - 141

SP - 670

EP - 677

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 4

ER -