Substance P induces inward current and regulates pacemaker currents through tachykinin NK1 receptor in cultured interstitial cells of Cajal of murine small intestine

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

Research output: Contribution to journalArticle

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Abstract

We investigated whether substance P modulates pacemaker currents generated in cultured interstitial cells of Cajal of murine small intestine using whole cell patch-clamp techniques at 30°C. Interstitial cells of Cajal generated spontaneous inward currents (pacemaker currents) at a holding potential of -70 mV. Tetrodotoxin, nifedipine, tetraethylammonium, 4-aminopyridine, or glibenclamide did not change the frequency and amplitude of pacemaker currents. However, divalent cations (Ni2+, Mn2+, Cd2+, and Co2+), nonselective cationic channel blockers (gadolinium and flufenamic acid), and a reduction of external Na+ from normal to 1 mM inhibited pacemaker currents indicating that nonselective cation channels are involved in their generation. Substance P depolarized the membrane potential in current clamp mode and produced tonic inward pacemaker currents with reduced frequency and amplitude in voltage clamp mode. [D-Arg1, D-Trp 7,9, Leu11] substance P, a tachykinin NK1 receptor antagonist, blocked these substance P-induced responses. Furthermore, [Sar9, Met(O2)11] substance P, a specific tachykinin NK1 receptor agonist, depolarized the membrane and tonic inward currents mimicked those of substance P. Substance P continued to produce tonic inward currents in external Ca2+-free solution or in the presence of chelerythrine, a protein kinase C inhibitor. However, substance P-induced tonic inward currents were blocked by thapsigargin, a Ca 2+-ATPase inhibitor in the endoplasmic reticulum or by an external 1 mM Na+ solution. Our results demonstrate that substance P may modulate intestinal motility by acting on the interstitial cells of Cajal by activating nonselective cation channels via the release of intracellular Ca 2+ induced by tachykinin NK1 receptor stimulation.

Original languageEnglish
Pages (from-to)35-42
Number of pages8
JournalEuropean Journal of Pharmacology
Volume495
Issue number1
DOIs
Publication statusPublished - 2004 Jul 8

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Tachykinin Receptors
Interstitial Cells of Cajal
Substance P
Small Intestine
Cultured Cells
Cations
Flufenamic Acid
4-Aminopyridine
Gastrointestinal Motility
Tetraethylammonium
Thapsigargin
Protein C Inhibitor
Glyburide
Divalent Cations
Tetrodotoxin
Gadolinium
Patch-Clamp Techniques
Nifedipine
Protein Kinase Inhibitors
Endoplasmic Reticulum

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Jun, Jae Yeoul ; Choi, Seok ; Yeum, Cheol Ho ; Chang, In Youb ; You, Ho Jin ; Park, Chan Kuk ; Kim, Man Yoo ; Kong, In Deok ; Kim, Min Ji ; Lee, Kyu Pil ; So, Insuk ; Kim, Ki Whan. / Substance P induces inward current and regulates pacemaker currents through tachykinin NK1 receptor in cultured interstitial cells of Cajal of murine small intestine. In: European Journal of Pharmacology. 2004 ; Vol. 495, No. 1. pp. 35-42.
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title = "Substance P induces inward current and regulates pacemaker currents through tachykinin NK1 receptor in cultured interstitial cells of Cajal of murine small intestine",
abstract = "We investigated whether substance P modulates pacemaker currents generated in cultured interstitial cells of Cajal of murine small intestine using whole cell patch-clamp techniques at 30°C. Interstitial cells of Cajal generated spontaneous inward currents (pacemaker currents) at a holding potential of -70 mV. Tetrodotoxin, nifedipine, tetraethylammonium, 4-aminopyridine, or glibenclamide did not change the frequency and amplitude of pacemaker currents. However, divalent cations (Ni2+, Mn2+, Cd2+, and Co2+), nonselective cationic channel blockers (gadolinium and flufenamic acid), and a reduction of external Na+ from normal to 1 mM inhibited pacemaker currents indicating that nonselective cation channels are involved in their generation. Substance P depolarized the membrane potential in current clamp mode and produced tonic inward pacemaker currents with reduced frequency and amplitude in voltage clamp mode. [D-Arg1, D-Trp 7,9, Leu11] substance P, a tachykinin NK1 receptor antagonist, blocked these substance P-induced responses. Furthermore, [Sar9, Met(O2)11] substance P, a specific tachykinin NK1 receptor agonist, depolarized the membrane and tonic inward currents mimicked those of substance P. Substance P continued to produce tonic inward currents in external Ca2+-free solution or in the presence of chelerythrine, a protein kinase C inhibitor. However, substance P-induced tonic inward currents were blocked by thapsigargin, a Ca 2+-ATPase inhibitor in the endoplasmic reticulum or by an external 1 mM Na+ solution. Our results demonstrate that substance P may modulate intestinal motility by acting on the interstitial cells of Cajal by activating nonselective cation channels via the release of intracellular Ca 2+ induced by tachykinin NK1 receptor stimulation.",
author = "Jun, {Jae Yeoul} and Seok Choi and Yeum, {Cheol Ho} and Chang, {In Youb} and You, {Ho Jin} and Park, {Chan Kuk} and Kim, {Man Yoo} and Kong, {In Deok} and Kim, {Min Ji} and Lee, {Kyu Pil} and Insuk So and Kim, {Ki Whan}",
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Substance P induces inward current and regulates pacemaker currents through tachykinin NK1 receptor in cultured interstitial cells of Cajal of murine small intestine. / Jun, Jae Yeoul; Choi, Seok; Yeum, Cheol Ho; Chang, In Youb; You, Ho Jin; Park, Chan Kuk; Kim, Man Yoo; Kong, In Deok; Kim, Min Ji; Lee, Kyu Pil; So, Insuk; Kim, Ki Whan.

In: European Journal of Pharmacology, Vol. 495, No. 1, 08.07.2004, p. 35-42.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Substance P induces inward current and regulates pacemaker currents through tachykinin NK1 receptor in cultured interstitial cells of Cajal of murine small intestine

AU - Jun, Jae Yeoul

AU - Choi, Seok

AU - Yeum, Cheol Ho

AU - Chang, In Youb

AU - You, Ho Jin

AU - Park, Chan Kuk

AU - Kim, Man Yoo

AU - Kong, In Deok

AU - Kim, Min Ji

AU - Lee, Kyu Pil

AU - So, Insuk

AU - Kim, Ki Whan

PY - 2004/7/8

Y1 - 2004/7/8

N2 - We investigated whether substance P modulates pacemaker currents generated in cultured interstitial cells of Cajal of murine small intestine using whole cell patch-clamp techniques at 30°C. Interstitial cells of Cajal generated spontaneous inward currents (pacemaker currents) at a holding potential of -70 mV. Tetrodotoxin, nifedipine, tetraethylammonium, 4-aminopyridine, or glibenclamide did not change the frequency and amplitude of pacemaker currents. However, divalent cations (Ni2+, Mn2+, Cd2+, and Co2+), nonselective cationic channel blockers (gadolinium and flufenamic acid), and a reduction of external Na+ from normal to 1 mM inhibited pacemaker currents indicating that nonselective cation channels are involved in their generation. Substance P depolarized the membrane potential in current clamp mode and produced tonic inward pacemaker currents with reduced frequency and amplitude in voltage clamp mode. [D-Arg1, D-Trp 7,9, Leu11] substance P, a tachykinin NK1 receptor antagonist, blocked these substance P-induced responses. Furthermore, [Sar9, Met(O2)11] substance P, a specific tachykinin NK1 receptor agonist, depolarized the membrane and tonic inward currents mimicked those of substance P. Substance P continued to produce tonic inward currents in external Ca2+-free solution or in the presence of chelerythrine, a protein kinase C inhibitor. However, substance P-induced tonic inward currents were blocked by thapsigargin, a Ca 2+-ATPase inhibitor in the endoplasmic reticulum or by an external 1 mM Na+ solution. Our results demonstrate that substance P may modulate intestinal motility by acting on the interstitial cells of Cajal by activating nonselective cation channels via the release of intracellular Ca 2+ induced by tachykinin NK1 receptor stimulation.

AB - We investigated whether substance P modulates pacemaker currents generated in cultured interstitial cells of Cajal of murine small intestine using whole cell patch-clamp techniques at 30°C. Interstitial cells of Cajal generated spontaneous inward currents (pacemaker currents) at a holding potential of -70 mV. Tetrodotoxin, nifedipine, tetraethylammonium, 4-aminopyridine, or glibenclamide did not change the frequency and amplitude of pacemaker currents. However, divalent cations (Ni2+, Mn2+, Cd2+, and Co2+), nonselective cationic channel blockers (gadolinium and flufenamic acid), and a reduction of external Na+ from normal to 1 mM inhibited pacemaker currents indicating that nonselective cation channels are involved in their generation. Substance P depolarized the membrane potential in current clamp mode and produced tonic inward pacemaker currents with reduced frequency and amplitude in voltage clamp mode. [D-Arg1, D-Trp 7,9, Leu11] substance P, a tachykinin NK1 receptor antagonist, blocked these substance P-induced responses. Furthermore, [Sar9, Met(O2)11] substance P, a specific tachykinin NK1 receptor agonist, depolarized the membrane and tonic inward currents mimicked those of substance P. Substance P continued to produce tonic inward currents in external Ca2+-free solution or in the presence of chelerythrine, a protein kinase C inhibitor. However, substance P-induced tonic inward currents were blocked by thapsigargin, a Ca 2+-ATPase inhibitor in the endoplasmic reticulum or by an external 1 mM Na+ solution. Our results demonstrate that substance P may modulate intestinal motility by acting on the interstitial cells of Cajal by activating nonselective cation channels via the release of intracellular Ca 2+ induced by tachykinin NK1 receptor stimulation.

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