Role of capsaicin-sensitive afferent neurons in mucosal blood flow response of rat stomach induced by mild irritants

Matsumoto, Jiro; Takeuchi, Koji; Ueshima, Koji; Okabe, Susumu

doi:10.1007/bf01296001

Cited by 57 publications

(40 citation statements)

References 25 publications

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“…It has been shown that such GMBF responses in the stomach after damage are mediated by capsaicin-sensitive neurons as well as endogenous prostaglandins (PGs) (22). We confirmed that the increase in GMBF caused by TC was significantly reduced in capsaicin-pretreated rats.…”

Section: Discussionsupporting

confidence: 76%

Desensitization of Capsaicin-Sensitive Sensory Neurons in Rat Stomachs on Chronic Treatment with Sodium Taurocholate

Narita

Takahashi

Takeuchi

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-We examined the effects of chronic treatment with 10 mM sodium taurocholate (TC) on gastric functions, capsaicin-sensitive afferent neurons and the gastric mucosa in male rats. Stomachs were mounted in Lucite chambers, and then the transmucosal potential difference (PD), luminal pH and gastric mucosal blood flow (GMBF) in response to TC or capsaicin was determined. In normal animals, 10 mM TC caused a reduction in PD, and increases in luminal pH and GMBF. Capsaicin (1 mg/ml) produced an apparent increase in GMBF without any change in PD or luminal pH. After 4-or 12-week treatment with TC, the basal PD was significantly reduced, and the luminal pH tended to increase. The increase in GMBF in response to TC or capsaicin was profoundly suppressed in TC-pretreated animals. The calcitonin generelated peptide release in response to capsaicin was significantly reduced after 4 weeks treatment with TC. There were no microscopical changes in the oxyntic mucosa until 4 weeks after TC treatment except for exfoliation of surface cells. However, an increase in inflammatory cell infiltration was observed 12 weeks later. We conclude that chronic treatment with TC causes desensitization of capsaicin-sensitive afferent neurons and reduces GMBF, which may result in the production of gastritis.Keywords: Gastritis, Sodium taurocholate, Capsaicin-sensitive afferent neuron, Calcitonin gene-related peptide, Gastric mucosal blood flow Chronic treatment with 5 mM sodium taurocholate (TC) for >3 months induces gastritis in rats (1, 2). We also observed that treatment of rats having undergone unilateral vagotomy with 5 mM TC for 6 months induced gastritis that involved decreases in the number and density of parietal cells and an increase in inflammatory cell infiltration (3). The mechanism by which chronic treatment with TC results in such gastritis remains unclear. There is increasing evidence that capsaicin-sensitive afferent neurons (capsaicin-sensitive neurons) participate in the protective mechanism against acute gastritis or gastric ulceration (4-7), probably through the release of the calcitonin gene-related peptide (CGRP) (8 -10). Therefore, it is possible that acute or chronic depletion of CGRP from the gastric or duodenal mucosa may weaken the mucosal integrity, leading to the production of gastritis and ulcers. Indeed, ulcerogens such as acetic acid, concentrated ethanol and cysteamine significantly depleted CGRP from the peripheral endings of capsaicin-sensitive neurons, suggesting a causal relationship (11-13). It was of interest to examine whether or not chronic treatment with TC has any damaging effect on capsaicin-sensitive neurons which leads to disturbance of gastric functions, thereby eventually resulting in the production of gastritis. In this study, we determined the changes in gastric functions, the amount of CGRP released from the gastric mucosa and gastric mucosal histology in TC-treated animals. An abstract of part of this study has already been published (14). MATERIALS AND METHODS AnimalsMale Donryu rats ...

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Section: Discussionsupporting

confidence: 76%

Desensitization of Capsaicin-Sensitive Sensory Neurons in Rat Stomachs on Chronic Treatment with Sodium Taurocholate

Narita

Takahashi

Takeuchi

et al. 1995

Japanese Journal of Pharmacology

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“…The increase of luminal pH in the stomach exposed to mild irritants is considered to be due to both inhibition of acid secretion and diffusion of HC03 (17), while the GMBF response may be mediated by endogenous PGs and capsaicin-sensitive sensory neu rons (11,18). To our surprise, the increase of luminal pH after exposure to L-arginine was markedly inhibited by the NO biosynthesis inhibitor L-NAME, despite the fact that other parameters remained unaffected.…”

Section: Discussionmentioning

confidence: 57%

Cytoprotective Action of L-Arginine against HCl-Induced Gastric Injury in Rats: Involvement of Nitric Oxide?

Takeuchi

Ohuchi

Kato

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-We examined the cytoprotective effect of L-arginine on gastric damage induced by 0.6 N HC1 in rats and investigated whether the mechanism of this action is related to the nitric oxide (NO)-mediated protection. The animals were given 0.6 N HCI by gavage and killed 1 hr later. L-Arginine (100, 300 and 750 mg/kg) given p.o. 30 min before HC1 treatment prevented these lesions in a dose-dependent manner, but had no effect when given i.v. (200 mg/kg). Similar effects were observed by D-arginine but not by an equimolar dose of mannitol. This effect of L-arginine (p.o.) was attenuated significantly by prior administra tion of indomethacin (5 mg/kg, s.c.) but not by NG-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg, i.v.), the NO synthase inhibitor. Both L and D-arginine produced a reduction in potential difference (PD), inhibi tion of gastric motility, and increases of luminal pH and mucosal blood flow when they were given intra gastrically. Indomethacin significantly mitigated these changes induced by L-arginine except PD reduction, while L-NAME showed significant inhibition only against the increased pH response. We conclude that L arginine given p.o. exhibits gastric cytoprotection against HCl-induced damage in rats, probably by acting as a mild irritant. The mechanism of this action may appear through "adaptive cytoprotection" mediated by endogenous prostaglandins and does not involve the NO-mediated protective pathway.

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“…Although gastric hyperemia is not the exclusive mechanism of gastric cytoprotection as induced by PGE 2 or capsaicin-sensitive afferent neurons (Stroff et al, 1996;Araki et al, 2000), GMBF is considered to be a factor in capsaicin-induced gastric protection under certain experimental conditions (Holzer et al, 1991;Takeuchi et al, 1993). We previously reported that the gastric hyperemic response to capsaicin was also significantly mitigated by indomethacin, suggesting an involvement of endogenous PGs in this action (Matsumoto et al, 1992). In the present study, we confirmed that intragastric capsaicin caused a marked increase of GMBF in wildtype mice, in an indomethacin-sensitive manner.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that intragastric capsaicin increases GMBF in the rat stomach, and this effect is attenuated by sensory deafferentation after capsaicin pretreatment (Holzer et al, 1991;Matsumoto et al, 1992;Brzozowski et al, 1993). Although gastric hyperemia is not the exclusive mechanism of gastric cytoprotection as induced by PGE 2 or capsaicin-sensitive afferent neurons (Stroff et al, 1996;Araki et al, 2000), GMBF is considered to be a factor in capsaicin-induced gastric protection under certain experimental conditions (Holzer et al, 1991;Takeuchi et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…Because the gastroprotective action of capsaicin in certain experimental conditions is functionally related with the increase of GMBF (Holzer et al, 1991;Matsumoto et al, 1992;Brzozowski et al, 1996), we examined the gastric hyperemic response to capsaicin in mice and investigated the relation of this action with IP receptors. In addition, we also examined the effect of cicaprost, the PGI 2 agonist on GMBF, to check the absence of IP receptors in IP receptor knockout mice used in the present study.…”

Section: Effect Of Capsaicin On Gastric Mucosal Blood Flow In Micementioning

confidence: 99%

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Facilitation by Endogenous Prostaglandins of Capsaicin-Induced Gastric Protection in Rodents through EP2 and IP Receptors

Takeuchi¹,

Kato²,

Takeeda³

et al. 2002

J Pharmacol Exp Ther

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We investigated the role that prostaglandins (PGs) and EP receptors play in facilitating the gastroprotective action of capsaicin against HCl/ethanol in rats and mice. Male SpragueDawley rats and C57BL/6 mice were used after 18 h of fasting. The animals were given HCl/ethanol (60% in 150 mM HCl) p.o. and killed 1 h later. Capsaicin or various EP agonists were given p.o. 30 min or i.v. 10 min before HCl/ethanol. In some cases, indomethacin or various EP agonists were given s.c. 30 min or i.v 10 min before capsaicin, respectively. Gastric lesions induced by HCl/ethanol were significantly inhibited by PGE 2 as well as capsaicin. The effect of PGE 2 was antagonized by ONO-AE-829 (EP1 antagonist), whereas the capsaicin action was mitigated by indomethacin as well as sensory deafferentation but not by ONO-AE-829. The generation of mucosal PGE 2 was not affected by either capsaicin or sensory deafferentation, but was significantly inhibited by indomethacin. Although neither butaprost (EP2), ONO-NT-012 (EP3), nor 11-deoxy PGE1 (EP4) alone had any effect on HCl/ethanolinduced gastric lesions, only butaprost restored the protective action of capsaicin in the presence of indomethacin. Capsaicin provided a protective action against HCl/ethanol-induced gastric lesions in wild-type (ϩ/ϩ) mice in an indomethacin-sensitive manner, and this action was similarly observed in EP1 (Ϫ/Ϫ) and EP3 (Ϫ/Ϫ) mice but not in the animals lacking IP receptors. These results suggest that capsaicin exhibits gastric cytoprotection, essentially by stimulating sensory neurons, and this action is facilitated by endogenous PGs through EP2/IP receptors, probably sensitizing the sensory neurons to capsaicin.

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Role of capsaicin-sensitive afferent neurons in mucosal blood flow response of rat stomach induced by mild irritants

Cited by 57 publications

References 25 publications

Desensitization of Capsaicin-Sensitive Sensory Neurons in Rat Stomachs on Chronic Treatment with Sodium Taurocholate

Desensitization of Capsaicin-Sensitive Sensory Neurons in Rat Stomachs on Chronic Treatment with Sodium Taurocholate

Cytoprotective Action of L-Arginine against HCl-Induced Gastric Injury in Rats: Involvement of Nitric Oxide?

Facilitation by Endogenous Prostaglandins of Capsaicin-Induced Gastric Protection in Rodents through EP2 and IP Receptors

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