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

doi:10.1016/j.ejphar.2004.05.022

Cited by 40 publications

(28 citation statements)

References 26 publications

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“…It is well known that the periodic pacemaker activity of ICC is dependent on [Ca 2＋ ]i oscillation and that this pacemaker mechanism is initiated by the release of Ca 2＋ from the endoplasmic reticulum through the inositol triphosphate (IP3) receptor followed by re-uptake of Ca 2＋ into the mitochondria [16,17]. In previous reports, we also showed the pacemaker currents were abolished in Ca 2＋ -free solution [18]. Moreover, we could see that thapsigargin, a Ca 2＋ -ATPase inhibitor of endoplasmic reticulum and FCCP, an inhibitor of mitochondrial Ca 2＋ uptake, blocked the pacemaker activity of ICC, as did the NaHS-induced action in this study.…”

Section: Discussionmentioning

confidence: 83%

The Inhibitory Effects of Hydrogen Sulfide on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

Parajuli

Choi

Lee

et al. 2010

Korean J Physiol Pharmacol

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In this study, we studied whether hydrogen sulfide (H2S) has an effect on the pacemaker activity of interstitial cells of Cajal (ICC), in the small intestine of mice. The actions of H2S on pacemaker activity were investigated using whole-cell patch-clamp technique, intracellular Ca 2＋ analysis at 30 o C and RT-PCR in cultured mouse intestinal ICC. Exogenously applied sodium hydrogen sulfide (NaHS), a donor of hydrogen sulfide, caused a slight tonic inward current on pacemaker activity in ICC at low concentrations (50 and 100 μM), but at high concentration (500 μM and 1 mM) it seemed to cause light tonic inward currents and then inhibited pacemaker amplitude and pacemaker frequency, and also an increase in the resting currents in the outward direction. Glibenclamide or other potassium channel blockers (TEA, BaCl2, apamin or 4-aminopydirine) did not have an effect on NaHS-induced action in ICC. The exogenous application of carbonilcyanide p-triflouromethoxyphenylhydrazone (FCCP) and thapsigargin also inhibited the pacemaker activity of ICC as NaHS. Also, we found NaHS inhibited the spontaneous intracellular Ca 2＋ ([Ca 2＋ ]i) oscillations in cultured ICC. In doing an RT-PCR experiment, we found that ICC enriched population lacked mRNA for both CSE and CBS, but was prominently detected in unsorted muscle. In conclusion, H2S inhibited the pacemaker activity of ICC by modulating intracellular Ca 2＋ . These results can serve as evidence of the physiological action of H2S as acting on the ICC in gastrointestinal (GI) motility.

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Section: Discussionmentioning

confidence: 83%

The Inhibitory Effects of Hydrogen Sulfide on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

Parajuli

Choi

Lee

et al. 2010

Korean J Physiol Pharmacol

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“…The initial phase of the pacemaker potentials is sensitive to Ni 2+ (Tomita et al, 1998;Hirst and Edwards, 2001;Kito and Suzuki, 2003b), and is also inhibited by the reduction of [Ca 2+ ]o concentrations or by depolarization of the membrane Kito and Suzuki, 2003b), suggesting that it is formed by the activation of voltage-sensitive, but nifedipine-insensitive, Ca 2+ -permeable channels. In cultured ICC-MY isolated from the mouse small intestine, the ionic mechanism for generating the pacemaker currents is equivocal, and the possible involvement of Ca 2+ -sensitive Cl --channels (Tokutomi et al, 1995), non-selective cation channels (Thomsen et al, 1998) or Ca 2+ -inhibited non-selective cation channels (Koh et al, 2002) Jun et al, 2004). However in intact tissues isolated from the mouse intestine, the initial component of the pacemaker potential recorded from ICC-MY is inhibited by mibefradil, a non-selective inhibitor of voltagedependent Ca 2+ channels (Kito et al, 2005), while the plateau component is inhibited by chemicals known to inhibit the Ca 2+ -sensitive Cl --channels (Kito and Suzuki, 2003a).…”

Section: Discussionmentioning

confidence: 99%

The effects of flufenamic acid on spontaneous activity of smooth muscle tissue isolated from the guinea-pig stomach antrum

Hotta

Kito

Suzuki

2005

J. Smooth Muscle Res.

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The effects of flufenamic acid were investigated on slow waves, follower potentials and pacemaker potentials recorded respectively from circular smooth muscle cells, longitudinal smooth muscle cells and interstitial cells of Cajal distributed in the myenteric layers (ICC-MY) of the guinea-pig stomach antrum. Flufenamic acid (>10 -5 M)inhibited the amplitude and rate of rise of the upstroke phase of the slow waves, with no marked alteration in their frequency of occurrence. The inhibitory actions of flufenamic acid appeared to be mainly on slow potentials recorded from circular smooth muscle cells, but not on follower or pacemaker potentials. After abolishing spontaneous slow potentials with flufenamic acid, depolarizing current stimuli could evoke slow potentials with an amplitude that was much smaller than in the absence of flufenamic acid, with no significant alteration to the input resistance of the membrane. The time elapsed for the generation of the 2 nd component of the slow waves or the slow potentials evoked during depolarizing current pulse stimulation was increased by flufenamic acid. The rate of rise of unitary potentials, but not the frequency of occurrence, was inhibited by flufenamic acid. These results indicate that the inhibitory actions of flufenamic acid appear to be mainly on the circular muscle layer including the interstitial cells of Cajal distributed within the muscle bundles (ICC-IM). Nifedipine-sensitive spike potentials were not inhibited by flufenamic acid. It is concluded that the selective inhibition of the 2 nd component of slow waves by flufenamic acid may be mainly due to the inhibition of ion channels, possibly Ca 2+ -sensitive Cl --channels, activated during generation of slow potentials in the ICC-IM distributed in the circular muscle layer.

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“…Functional studies on cultured ICC from the mouse intestine showed that SP may modulate intestinal motility by acting on ICC via the release of intracellular Ca +2 induced by NK1r stimulation [78]. The authors, however, did not specify which types of ICC were cultured.…”

Section: Intestinal Icc In Culturementioning

confidence: 99%

Relationships between neurokinin receptor‐expressing interstitial cells of Cajal and tachykininergic nerves in the gut

Faussone–Pellegrini

2006

J Cellular Molecular Medi

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The so-called interstitial cells of Cajal (ICC) are distributed throughout the muscle coat of the alimentary tract with characteristic intramural location and species-variations in structure and staining. Several ICC sub-types have been identified: ICC-DMP, ICC-MP, ICC-IM, ICC-SM. Gut motility is regulated by ICC and each sub-type is responsible for the electrical activities typical of each gut region and/or muscle layer. The interstitial position of the ICC between nerve endings and smooth muscle cells has been extensively considered. Some of these nerve endings contain tachykinins. Three distinct tachykinin receptors (NK1r, NK2r and NK3r) have been demonstrated by molecular biology. Each of them binds with different affinities to a series of tachykinins (SP, NKA and NKB). In the ileum, SP-immunoreactive (SP-IR) nerve fibers form a rich plexus at the deep muscular plexus (DMP), distributed around SP-negative cells, and ICC-DMP intensely express the SP-preferred receptor NK1r; conversely a faint NK1r-IR is detected on the ICC-MP and mainly after receptor internalization was induced by agonists. ICC-IM are never stained in laboratory mammals, while those of the human antrum are NK1r-IR. RT-PCR conducted on isolated ileal ICC-MP and gastric ICC-IM showed that these cells express NK1r and NK3r. Colonic ICC, except those in humans, do not express NK1r-IR, at least in resting conditions. Outside the gut, NK1r-IR cells were seen in the arterial wall and exocrine pancreas. In the mouse gut only, NK1r-IR is present in non-neuronal cells located within the intestinal villi, so-called myoid cells, which are c-kit-negative and α-smooth muscle actin-positive. Immunohistochemistry and functional studies confirmed that ICC receive input from SP-IR terminals, with differences between ICC sub-types. In the rat, very early after birth, NK1r is expressed by the ICC-DMP and SP by the related nerve varicosities. Studies on pathological conditions are few and those on mutant strains practically absent. It has only been reported that in the inflamed ileum of rats the NK1r-IR ICC-DMP disappear and that at the peak of inflammatory conditions ICC-MP are NK1r-IR. In the ileum of mice with a mutation in the W locus, ICC-DMP were seen to express c-kit-IR but not NK1-IR, and SP-IR innervation seems unchanged. In summary, there are distinct ICC populations, each of them under a different tachykininergic control and, likely, having different functions. Further studies are recommended at the aim of understanding ICC involvement in modulating/transmitting tachykininergic inputs.

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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

Cited by 40 publications

References 26 publications

The Inhibitory Effects of Hydrogen Sulfide on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

The Inhibitory Effects of Hydrogen Sulfide on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

The effects of flufenamic acid on spontaneous activity of smooth muscle tissue isolated from the guinea-pig stomach antrum

Relationships between neurokinin receptor‐expressing interstitial cells of Cajal and tachykininergic nerves in the gut

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