Capsaicin-induced, capsazepine-insensitive relaxation of the guinea-pig ileum

Fujimoto, Seigo; Mori, Mayumi; Tsushima, Hiromi; Kunimatsu, Mitoshi

doi:10.1016/j.ejphar.2005.11.011

Cited by 25 publications

(29 citation statements)

References 43 publications

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“…Therefore, the fact that zingerone inhibited colonic motility even after enhancing spontaneous motility by tetrodotoxin shows that the inhibition of colonic motility by zingerone is not due to its action on the enteric nervous system but due to a direct action on smooth muscles. In accordance with this, direct inhibitory effects on smooth muscles have been reported for some pungent compounds, including capsaicin and piperine [22][23][24][25][26]. The direct actions on smooth muscles have been shown to be independent of TRPV1 [24][25][26][27], being consistent with the fact that zingeroneinduced inhibition of colonic motility was resistant to a TRPV1 antagonist.…”

Section: Discussionsupporting

confidence: 51%

Inhibitory effects of zingerone, a pungent component of Zingiber officinale Roscoe, on colonic motility in rats

Iwami

Shiina²,

Hirayama³

et al. 2010

J Nat Med

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Ginger (rhizome of Zingiber officinale Roscoe) is an herbal medicine for the treatment of gastrointestinal disorders including constipation and diarrhea. Zingerone is a likely active constituent responsible for the antidiarrheal activity of ginger. The current study was designed to characterize pharmacological actions of zingerone on colonic motility. To evaluate pharmacological effects of zingerone on colonic motility, we used isolated colonic segments from rats, in which mechanical responses were recorded in the longitudinal direction. In addition, we evaluated the effects on colonic motility in vivo by measuring intraluminal pressure changes and expelled fluid volume from the colon in anesthetized rats. Zingerone was applied to the lumen of the colon to allow the drug to access from the mucosal side. Zingerone inhibited spontaneous contractile movements in the isolated colonic segments in a dose-dependent manner. The inhibitory effects of zingerone on colonic movements were not affected by pretreatment with capsazepine, a typical antagonist of transient receptor potential vanilloid 1. In addition, tetrodotoxin, a blocker of voltage-dependent sodium channels on neurons, did not affect the suppression of colonic movements by zingerone, suggesting that zingerone acts on the smooth muscles directly. Zingerone also attenuated colonic motility in vivo without affecting blood pressure and heart rate. The effects were reversible and reproducible. Our findings suggest that zingerone can inhibit colonic motility via direct action on smooth muscles. Zingerone might exert beneficial therapeutic effects on hypermotility-induced diarrhea by abrogating excessive gastrointestinal motility.

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Section: Discussionsupporting

confidence: 51%

Inhibitory effects of zingerone, a pungent component of Zingiber officinale Roscoe, on colonic motility in rats

Iwami

Shiina²,

Hirayama³

et al. 2010

J Nat Med

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“…In Calu-3 cells, both capsaicin and capsazepine blocked the FSK-I sc via a Rho-kinase-dependent pathway (26). In guinea pig ileal longitudinal smooth muscle, capsaicin induced a capsazepine-insensitive relaxation that was 4-aminopyridine and high KCl-sensitive (17). Similarly, capsaicin induced a vasodilatation of nasal vasculature that was capsazepine-insensitive, but affected by blockers of COX-2 and the prostanoid receptor (62).…”

Section: Discussionmentioning

confidence: 87%

Capsaicin induces NKCC1 internalization and inhibits chloride secretion in colonic epithelial cells independently of TRPV1

Bouyer

Tang

Weber

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Colonic chloride secretion is regulated via the neurohormonal and immune systems. Exogenous chemicals (e.g., butyrate, propionate) can affect chloride secretion. Capsaicin, the pungent ingredient of the chili peppers, exerts various effects on gastrointestinal function. Capsaicin is known to activate the transient receptor potential vanilloid type 1 (TRPV1), expressed in the mesenteric nervous system. Recent studies have also demonstrated its presence in epithelial cells but its role remains uncertain. Because capsaicin has been reported to inhibit colonic chloride secretion, we tested whether this effect of capsaicin could occur by direct action on epithelial cells. In mouse colon and model T84 human colonic epithelial cells, we found that capsaicin inhibited forskolin-dependent short-circuit current (FSK-I(sc)). Using PCR and Western blot, we demonstrated the presence of TRPV1 in colonic epithelial cells. In T84 cells, TRPV1 localized at the basolateral membrane and in vesicular compartments. In permeabilized monolayers, capsaicin activated apical chloride conductance, had no effect on basolateral potassium conductance, but induced NKCC1 internalization demonstrated by immunocytochemistry and basolateral surface biotinylation. AMG-9810, a potent inhibitor of TRPV1, did not prevent the inhibition of the FSK-I(sc) by capsaicin. Neither resiniferatoxin nor N-oleoyldopamine, two selective agonists of TRPV1, blocked the FSK-I(sc). Conversely capsaicin, resiniferatoxin, and N-oleoyldopamine raised intracellular calcium ([Ca(2+)](i)) in T84 cells and AMG-9810 blocked the rise in [Ca(2+)](i) induced by capsaicin and resiniferatoxin suggesting the presence of a functional TRPV1 channel. We conclude that capsaicin inhibits chloride secretion in part by causing NKCC1 internalization, but by a mechanism that appears to be independent of TRPV1.

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“…ATP-sensitive K ϩ (K ATP ) channel. Similarly, Fujimoto et al (13) reported that capsaicin-mediated relaxation of guinea pig ileum via voltage-dependent K ϩ channels. Presently, we found that TEA and IBTX (BK channels) administration attenuated capsaicin relaxation responses (Fig.…”

Section: Discussionmentioning

confidence: 95%

Impaired capsaicin-induced relaxation of coronary arteries in a porcine model of the metabolic syndrome

Bratz¹,

Dick²,

Tune³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

116

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Recent studies implicate channels of the transient receptor potential vanilloid family (e.g., TRPV1) in regulating vascular tone; however, little is known about these channels in the coronary circulation. Furthermore, it is unclear whether metabolic syndrome alters the function and/or expression of TRPV1. We tested the hypothesis that TRPV1 mediates coronary vasodilation through endothelium-dependent mechanisms that are impaired by the metabolic syndrome. Studies were conducted on coronary arteries from lean and obese male Ossabaw miniature swine. In lean pigs, capsaicin, a TRPV1 agonist, relaxed arteries in a dose-dependent manner (EC50 = 116 +/- 41 nM). Capsaicin-induced relaxation was blocked by the TRPV1 antagonist capsazepine, endothelial denudation, inhibition of nitric oxide synthase, and K+ channel antagonists. Capsaicin-induced relaxation was impaired in rings from pigs with metabolic syndrome (91 +/- 4% vs. 51 +/- 10% relaxation at 100 microM). TRPV1 immunoreactivity was prominent in coronary endothelial cells. TRPV1 protein expression was decreased 40 +/- 11% in obese pigs. Capsaicin (100 microM) elicited divalent cation influx that was abolished in endothelial cells from obese pigs. These data indicate that TRPV1 channels are functionally expressed in the coronary circulation and mediate endothelium-dependent vasodilation through a mechanism involving nitric oxide and K+ channels. Impaired capsaicin-induced vasodilation in the metabolic syndrome is associated with decreased expression of TRPV1 and cation influx.

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Capsaicin-induced, capsazepine-insensitive relaxation of the guinea-pig ileum

Cited by 25 publications

References 43 publications

Inhibitory effects of zingerone, a pungent component of Zingiber officinale Roscoe, on colonic motility in rats

Inhibitory effects of zingerone, a pungent component of Zingiber officinale Roscoe, on colonic motility in rats

Capsaicin induces NKCC1 internalization and inhibits chloride secretion in colonic epithelial cells independently of TRPV1

Impaired capsaicin-induced relaxation of coronary arteries in a porcine model of the metabolic syndrome

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