Neurotensin Modulates Pacemaker Activity in Interstitial Cells of Cajal from the Mouse Small Intestine

Lee, Jun; Park, Chan Guk; Kim, Man Yoo; Chang, In Yeoub; Zuo, Dong; Shahi, Pawan K; Choi, Seok; Yeum, Cheol Ho; Jun, Jae Yeoul

doi:10.1007/s10059-012-2290-5

Cited by 14 publications

(9 citation statements)

References 31 publications

(28 reference statements)

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“…This study demonstrates that STO cells can support ICC in culture and maintains the spontaneous intracellular Ca 2+ oscillation frequency within the previously published range 16 , 18 , 26 , 37 – 39 , 44 – 46 . These functional ICC pace the rhythmic contractions of SMC.…”

Section: Discussionsupporting

confidence: 84%

Bioengineering functional smooth muscle with spontaneous rhythmic contraction in vitro

Kobayashi

Khalil

et al. 2018

Sci Rep

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Oriented smooth muscle layers in the intestine contract rhythmically due to the action of interstitial cells of Cajal (ICC) that serve as pacemakers of the intestine. Disruption of ICC networks has been reported in various intestinal motility disorders, which limit the quality and expectancy of life. A significant challenge in intestinal smooth muscle engineering is the rapid loss of function in cultured ICC and smooth muscle cells (SMC). Here we demonstrate a novel approach to maintain the function of both ICC and SMC in vitro. Primary intestinal SMC mixtures cultured on feeder cells seeded electrospun poly(3-caprolactone) scaffolds exhibited rhythmic contractions with directionality for over 10 weeks in vitro. The simplicity of this system should allow for wide usage in research on intestinal motility disorders and tissue engineering, and may prove to be a versatile platform for generating other types of functional SMC in vitro.

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Section: Discussionsupporting

confidence: 84%

Bioengineering functional smooth muscle with spontaneous rhythmic contraction in vitro

Kobayashi

Khalil

et al. 2018

Sci Rep

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“…Neurotensin receptors are abundant in the neural plexuses and in the musculature, but no evidence was found of the receptor on ICC in the mouse and human. 4 However, since the NTR1 is present on cultured ICC from mice where it modulates pacemaker currents, 5 there is a possibility that neurotensin can influence or modulate pacemaker currents in ICC-MP in the rat colon.…”

Section: Discussionmentioning

confidence: 99%

“…4 NTR1 were found on cultured ICC from mice and neurotensin modulated pacemaker currents via the activation of non-selective cation channels by intracellular Ca 2+ -release through NTR1. 5 The laboratory of Rosa Serio studied the action of neurotensin on a 2 cm isolated segment of the rat colon using intraluminal pressure measurements. Neurotensin (100 nM) produced an inhibitory effect mediated by nitric oxide and an excitatory effect that was inhibited by atropine.…”

Section: Introductionmentioning

confidence: 99%

Neurotensin Changes Propulsive Activity into a Segmental Motor Pattern in the Rat Colon

Chen

Yang

et al. 2016

J Neurogastroenterol Motil

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Background/AimsNeurotensin is a gut-brain peptide with both inhibitory and excitatory actions on the colonic musculature; our objective was to understand the implications of this for motor patterns occurring in the intact colon of the rat. MethodsThe effects of neurotensin with concentrations ranging from 0.1-100 nM were studied in the intact rat colon in vitro, by investigating spatio-temporal maps created from video recordings of colonic motility before and after neurotensin. ResultsLow concentration of neurotensin (0.1-1 nM) inhibited propagating long distance contractions and rhythmic propagating motor complexes; in its place a slow propagating rhythmic segmental motor pattern developed. The neurotensin receptor 1 antagonist SR-48692 prevented the development of the segmental motor pattern. Higher concentrations of neurotensin (10 nM and 100 nM) were capable of restoring long distance contraction activity and inhibiting the segmental activity. The slow propagating segmental contraction showed a rhythmic contraction --relaxation cycle at the slow wave frequency originating from the interstitial cells of Cajal associated with the myenteric plexus pacemaker. High concentrations given without prior additions of low concentrations did not evoke the segmental motor pattern. These actions occurred when neurotensin was given in the bath solution or intraluminally. The segmental motor pattern evoked by neurotensin was inhibited by the neural conduction blocker lidocaine. ConclusionsNeurotensin (0.1-1 nM) inhibits the dominant propulsive motor patterns of the colon and a distinct motor pattern of rhythmic slow propagating segmental contractions develops. This motor pattern has the hallmarks of haustral boundary contractions. (J Neurogastroenterol Motil 2016;22:517-528)

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“…FFA modulates gastrointestinal tract motility by reducing pacemaker potentials of intestinal cells of Cajal in mice (Han et al ., 2012; Lee et al ., 2012). This effect has also been observed at 50 μM in human intestinal cells of Cajal and attributed to the inhibition of the TRPM7 channel (Kim et al ., 2009).…”

Section: Impact Of Ion Channels Modulation By Ffa On Physiologicalmentioning

confidence: 99%

Flufenamic acid as an ion channel modulator

Guinamard

Simard

Negro

2013

Pharmacology & Therapeutics

120

113

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Flufenamic acid has been known since the 1960s to have anti-inflammatory properties attributable to the reduction of prostaglandin synthesis. Thirty years later, flufenamic acid appeared to be an ion channel modulator. Thus, while its use in medicine diminished, its use in ionic channel research expanded. Flufenamic acid commonly affects non-selective cation channels and chloride channels, but also modulates potassium, calcium and sodium channels with effective concentrations ranging from 10-6 M in TRPM4 channel inhibition to 10-3 M in two-pore outwardly rectifying potassium channel activation. Because flufenamic acid effects develop and reverse rapidly, it is a convenient and widely used tool. However, given the broad spectrum of its targets, experimental results have to be interpreted cautiously. Here we provide an overview of ion channels targeted by flufenamic acid to aid in interpreting its effects at the molecular, cellular, and systems levels. If it is used with good practices, flufenamic acid remains a useful tool for ion channel research. Understanding the targets of FFA may help reevaluate its physiological impacts and revive interest in its therapeutic potential.

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Neurotensin Modulates Pacemaker Activity in Interstitial Cells of Cajal from the Mouse Small Intestine

Cited by 14 publications

References 31 publications

Bioengineering functional smooth muscle with spontaneous rhythmic contraction in vitro

Bioengineering functional smooth muscle with spontaneous rhythmic contraction in vitro

Neurotensin Changes Propulsive Activity into a Segmental Motor Pattern in the Rat Colon

Flufenamic acid as an ion channel modulator

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