Wyniki wyszukiwania - Biblioteka Nauki

1

Gastric cytoprotection by prostaglandin E2 and prostacyclin: relationship to EP1 and IP receptors

100%

Takeuchi K.

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nr 1

2

Involvement of corticotropin-releasing factor and corticotropin-releasing factor 2 receptors in pathogenesis of ischemia/reperfusion-induced enteritis in rats

51%

Takeuchi K. , Kumano A. , Abe N. , Kotani T.

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nr 5

3

Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage

51%

Takeuchi K. , Tanaka A. , Ohno R. , Yokota A.

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nr 4

165-182

EN

Nonsteroidal antiinflammatory drugs (NSAIDs) such as indomethacin decrease mucosal PGE2 production by inhibiting cyclooxygenase (COX) activity and produce damage in the small intestine. The development of intestinal lesions as induced by indomethacin was accompanied by increases in intestinal motility, enterobacterial invasion, and myeloperoxidase (MPO) as well as inducible nitric oxide synthase (iNOS) activity, together with the up-regulation of COX-2 and iNOS mRNA expression. Neither the selective COX-1 inhibitor, SC-560, nor the selective COX-2 inhibitor, rofecoxib, alone caused intestinal damage, but their combined administration produced lesions. SC-560, but not rofecoxib, caused intestinal hypermotility, bacterial invasion and the expression of COX-2 as well as iNOS mRNAs, yet the iNOS and MPO activity was increased only when rofecoxib was administered together with SC-560. Although SC-560 inhibited the PG production, the level of PGE2 was recovered, in a rofecoxib-dependent manner. The intestinal hypermotility response to indomethacin was prevented by both 16,16-dimethyl PGE2 and atropine but not ampicillin, yet all these agents inhibited not only the bacterial invasion but also the expression of COX-2 as well as the iNOS activity in the intestinal mucosa following indomethacin treatment, resulting in preventing the intestinal lesions. These results suggest that inhibition of COX-1, despite causing intestinal hypermotility, bacterial invasion and iNOS expression, up-regulates the expression of COX-2, and the PGE2 derived from COX-2 counteracts deleterious events caused by COX-1 inhibition and maintains the mucosal integrity. These sequences of events explain why intestinal damage occurs when both COX-1 and COX-2 are inhibited.

4

ACE inhibitor and AT1 antagonist stimulate duodenal HCO3 secretion mediated by a common pathway - involvement of PG, NO and bradykinin

51%

Aihara E. , Kagawa S. , Hayashi M. , Takeuchi K.

Journal of Physiology and Pharmacology

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2005

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tom 56

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nr 3

EN

Recent study demonstrated that duodenal HCO3- secretion is affected by modulation of the renin-angiotensin system. We examined the effects of enalapril (angiotensin-converting enzyme (ACE) inhibitor) or losartan (angiotensin AT1 receptor antagonist) on duodenal HCO3- secretion in rats and investigated the mechanisms involved in the renin-angiotensin system-related HCO3- response. A proximal duodenal loop was perfused with saline, and HCO3- secretion was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. Enalapril increased the HCO3- secretion in a dose-dependent manner, with a decrease in arterial blood pressure (MBP), and these effects were significantly attenuated by pretreatment with indomethacin, L-NAME and FR172357 (a selective bradykinin B2 receptor antagonist). Although losartan alone did not affect the HCO3- secretion, despite reducing MBP, the agent dose-dependently increased the HCO3- secretion in the presence of angiotensin II, and this response was totally antagonized by prior administration of FR172357, indomethacin and L-NAME. Bradykinin also dose-dependently increased the HCO3- secretion with no change in MBP, though transient, and again the effects were blocked by indomethacin, L-NAME and FR172357. Both prostaglandin (PG) E2 and the nitric oxide (NO) donor NOR-3 also increased the HCO3- secretion, the latter effect being inhibited by indomethacin. These results suggest that both an ACE inhibitor and AT1 antagonist (in the presence of angiotensin II) increase duodenal HCO3- secretion via a common pathway, involving bradykinin, NO and PGs. It is also assumed that bradykinin releases NO locally, which in turns stimulates HCO3- secretion mediated by PGs.

5

Muscarinic acetylcholine receptor subtype 4 is esssential for cholinergic stimulation of duodenal bicarbonate secretion in mice - relationship to D cell/somatostatin

45%

Takeuchi K. , Kita K. , Takahashi K. , Aihara E. , Hayashi S.

Journal of Physiology and Pharmacology

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2015

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tom 66

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nr 3

6

Prophylactic effect of egualen sodium, a stable azulene derivative, on gastrointestinal damage induced by ischemia-reperfusion, double antiplatelet therapy and loxoprofen in rats

45%

Amagase K. , Yoshida Y. , Hara D. , Murakami T. , Takeuchi K.

Journal of Physiology and Pharmacology

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2013

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tom 64

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nr 1

7

Antral ulcers induced by alendronate, a nitrogen-containing bisphosphonate, in rat stomachs - prophylactic effect of rebamipide

45%

Ohashi Y. , Aihara E. , Takasuka H. , Takahashi K. , Takeuchi K.

Journal of Physiology and Pharmacology

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2009

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tom 60

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nr 3

85-93

EN

We demonstrated the development of antral ulcers induced in rats by alendronate and investigated the pathogenic factors involved in this model. Animals fasted for 18 h were given alendronate p.o., and then re-fed normally and killed on various days up to 7 days later. Alendronate caused non-hemorrhagic damage in both the corpus and antrum of fasted rats, but after refeeding for 3 days the lesions in the corpus healed completely, while those in the antrum developed into large ulcers with increased vascular permeability. The development of antral ulcers was accompanied by an increase in MPO activity and lipid peroxidation as well as a decrease in SOD activity and GSH content in the mucosa. Histologically, the damage did not penetrate the muscularis mucosa, yet severe edema and neutrophil infiltration were observed in the submucosa. Neither omeprazole nor indomethacin had any effect, while allopurinol and SOD reduced the severity of these ulcers. Rebamipide dose-dependently suppressed the ulcerogenic response to alendronate, with a concomitant reversal of the increased vascular permeability, MPO activity and lipid peroxidation as well as the reduced SOD activity and GSH content. These results suggest that alendronate did not cause gross damage in the stomach of fasted rats, yet produced large ulcers in the antrum with severe edema after refeeding. The pathogenesis of these ulcers may be explained by impairment of the mucosal anti-oxidative system and does not involve acid/peptic digestion and deficiency of prostaglandins. Rebamipide prevents the antral ulcers, probably due to its anti-oxidative as well as anti-inflammatory actions.

8

Role of endothelial nitric oxide synthase in aggravation of indomethacin-induced gastric damage in adjuvant arthritic rats

45%

Kato S. , Ohkawa F. , Ito Y. , Amagase K. , Takeuchi K.

Journal of Physiology and Pharmacology

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2009

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tom 60

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nr 4

147-155

EN

The role of nitric oxide synthase (NOS) isozymes in the aggravation of indomethacin-induced gastric damage in adjuvant arthritic rats was investigated. Two weeks after injection of Freund’s complete adjuvant, the animals were given indomethacin, and the stomach was examined for damage 4 h later. Indomethacin caused hemorrhagic lesions in the normal rat stomach, and these lesions were markedly aggravated in arthritic rats. Pretreatment with L-NAME (a nonselective inhibitor of NOS) and aminoguanidine (a relative selective inhibitor of iNOS) did not affect the ulcerogenic response in normal rats but dose-dependently prevented the aggravation of lesions in arthritic rats, but the effect of aminoguanidine was apparently less than that of L-NAME. The increased ulcerogenic response in arthritic rats was significantly suppressed by 1400 W (a selective inhibitor of iNOS) and L-NIO (a selective inhibitor of eNOS) but not by L-NPA (a selective inhibitor of nNOS). The concurrent administration of 1400 W and L-NIO almost totally abolished the aggravation of damage in arthritic rats. The expressions of eNOS and iNOS but not nNOS in the gastric mucosa were clearly enhanced in arthritic rats. Mucosal levels of non-protein sulfhydryls were significantly lower in arthritic rats than those in normal rats. The aggravation of damage in arthritic rats was significantly prevented by glutathione. These results suggest that the increased ulcerogenic response to indomethacin in arthritic rat stomachs is mediated by NO derived from eNOS in addition to iNOS. It is assumed that eNOS/NO may act harmfully on the gastric mucosa of arthritic rats with mucosal SH deficiency.

9

Roles of endogenous prostaglandins and cyclooxygenase isozymes in mucosal defense of inflamed rat stomach

45%

Takeeda M. , Hayashi Y. , Yamato M. , Murakami M. , Takeuchi K.

Journal of Physiology and Pharmacology

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2004

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tom 55

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nr 1,2

EN

Endogenous prostaglandins (PGs) are involved in adaptive gastric protection against acute injury, and cyclooxygenase (COX)-1 is responsible for the production of PGs in this phenomenon. In the present study, we examined the effect of various COX inhibitors on gastric ulcerogenic and acid secretory responses following daily exposure of the stomach to iodoacetamide (IA) and investigated the role for COX isozyme in gastric protection under subchronic mucosal irritation. Gastric mucosal irritation was induced by addition of 0.1% IA to drinking water, and the gastric mucosa was examined on the 6th day. Indomethacin (5 mg/kg) or SC-560 (selective COX-1 inhibitor, 5 mg/kg) or rofecoxib (selective COX-2 inhibitor, 5 mg/kg) was given p.o. twice 24 hr and 3 hr before the termination of IA treatment. Giving IA in drinking water for 5 days produced minimal damage in the stomach. The damage was significantly worsened by indomethacin, resulting in hemorrhagic lesions. Both SC-560 and rofecoxib also aggravated such lesions, although the effect of rofecoxib was more pronounced. Treatment with IA decreased acid secretion in pylorus-ligated stomachs, and this change was significantly reverted by indomethacin as well as SC-560 and rofecoxib. Mucosal PGE2 content was increased following IA treatment, with apparent expression of COX-2 mRNA in the stomach, and the increased PGE2 production was significantly suppressed by SC-560 and rofecoxib as well as indomethacin. These results suggest that endogenous PGs derived from both COX-1 and COX-2 are involved in the mucosal defense of the inflamed stomach, partly by decreasing acid secretion and contribute to maintaining the mucosal integrity under such conditions.

10

Stimulation by nitric oxide of gastric acid secretion in bullfrog fundic mucosa in vitro

45%

Kawauchi S. , Sugamoto S. , Furukawa O. , Mimaki H. , Takeuchi K.

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2001

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tom 52

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nr 1

11

Involvement of prostaglandin E receptor EP3 subtype and prostacyclin IP receptor in decreased acid response in damaged stomach

45%

Nishio H. , Terashima S. , Nakashima M. , Aihara E. , Takeuchi K.

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tom 58

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nr 3

EN

We investigated the roles of cyclooxygenase (COX) isozymes and prostaglandin E (PGE) receptor EP1 and EP3 subtypes or prostacyclin IP receptors in the decrease in acid secretion in the damaged mouse stomach. Male C57/BL6 mice, both wild type and animals lacking EP1, EP3, or IP receptors, were used after 18 h of fasting. Under urethane anesthesia, the stomach was mounted on an ex-vivo chamber and perfused with saline, and acid secretion as well as transmucosal potential difference (PD) was measured before and after exposure to 20 mM taurocholate Na (TC) for 20 min. Indomethacin, SC-560 or rofecoxib was given i.d. 30 min before TC. Mucosal exposure to TC in wild-type mice caused a reduction in PD, followed by decrease in acid secretion. Indomethacin attenuated the decrease in acid secretion after exposure to TC in wild-type mice, an effect mimicked by SC-560 but not rofecoxib, yet none of these drugs affected the decrease in PD. An altered acid response after exposure to TC was similarly observed in EP1 (-/-) mice but mitigated in mice lacking either EP3 or IP receptors, although a decrease in PD was observed in all groups. Furthermore, the decreased acid response was also attenuated by prior administration of the EP3- but not EP1- antagonist. Mucosal levels of PGE2 and 6-keto PGF1alpha increased after exposure to TC in all groups of mice. In conclusion, the decrease in acid secretion in the damaged stomach is mediated by endogenous PGs derived from COX-1, through PGE2/EP3 receptors and prostacyclin/IP receptors.

12

Involvement of cyclooxygenase-1, prostaglandin E2 and EP1 receptors in acid-induced HCO3- secretion in stomach

45%

Takeuchi K. , Aihara E. , Sasaki Y. , Nomura Y. , Ise F.

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2006

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tom 57

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nr 4

EN

We investigated the cyclooxygenase (COX) isoforms as well as prostaglandin E receptor EP subtypes responsible for acid-induced gastric HCO3- secretion in rats and EP receptor-knockout (-/-) mice. Under urethane anesthesia, a chambered stomach (in the presence of omeprazole) was perfused with saline, and HCO3-secretion was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. Mucosal acidification was achieved by exposing the stomach for 10 min to 50 or 100 mM HCl. Acidification of the mucosa increased the secretion of HCO3- in the stomach of both rats and WT mice, in an indomethacin-inhibitable manner. The acid-induced gastric HCO3- secretion was inhibited by prior administration of indomethacin and SC-560 but not rofecoxib in rats and mice. Acidification increased the PGE2 content of the rat stomach, and this response was significantly attenuated by indomethacin and SC-560 but not rofecoxib. This response was also attenuated by ONO-8711 (EP1 antagonist) but not AE3-208 (EP4 antagonist) in rats and disappeared in EP1 (-/-) but not EP3 (-/-) mice. PGE2 increased gastric HCO3- secretion in both rats and WT mice, and this action was inhibited by ONO-8711 and disappeared in EP1 (-/-) but not EP3 (-/-) mice. These results support a mediator role for endogenous PGs in the gastric response induced by mucosal acidification and clearly indicate that the enzyme responsible for production of PGs in this process is COX-1. They further show that the presence of EP1 receptors is essential for the increase in the secretion of HCO3- in response to mucosal acidification in the stomach.

13

Dual action of nitric oxide in pathogenesis of indomethacin-induced small intestinal ulceration in rats

45%

Tanaka A. , Kunikata T. , Mizoguchi H. , Kato S. , Takeuchi K.

Journal of Physiology and Pharmacology

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1999

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tom 50

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nr 3

14

Role of macrophage colony-stimulating factor (M-CSF)-dependent macrophages in gastric ulcer healing in mice

38%

Kawahara Y. , Nakase Y. , Isomoto Y. , Matsuda N. , Amagase K. , Kato S. , Takeuchi K.

Journal of Physiology and Pharmacology

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2011

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tom 62

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nr 4

15

Gastric ulcerogenic and healing impairment effects of risedronate, a nitrogen-containing bisphosphonate in rats. Comparison with alendronate and minodronate

38%

Amagase K. , Inaba A. , Senta T. , Ishikawa Y. , Nukui K. , Murakami T. , Takeuchi K.

Journal of Physiology and Pharmacology

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2011

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tom 62

|

nr 6

16

A new model of gastric bleeding induced in rats by aspirin plus clopidogrel under stimulation of acid secretion. Prophylactic effects of antiulcer drugs

38%

Takayama S. , Izuhara C. , Yamada N. , Yamanaka S. , Hashimoto E. , Kaneko S. , Takeuchi K.

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2012

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tom 63

|

nr 1

17

Cinacalcet, a calcimimetic, prevents nonsteroidal antiinflammatory drug-induced small intestinal damage in rats

38%

Hayashi S. , Kurata N. , Kitahirachi E. , Nishimura Y. , Amagase K. , Yano T. , Takeuchi K.

Journal of Physiology and Pharmacology

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2013

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tom 64

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nr 4

18

Roles of nitric oxide (NO) and NO synthases in healing of dextran sulfate sodium-induced rat colitis

38%

Aoi Y. , Terashima S. , Ogura M. , Nishio H. , Kato S. , Takeuchi K.

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tom 59

|

nr 2

EN

We examined the effects of various NO inhibitors on the healing of DSS-induced rat colitis. Experimental colitis was induced by feeding rats for 6 days with 2.5% DSS in drinking water. After DSS treatment, the animals were fed normally and killed various days up to 7 days later. L-NAME (a nonselective NOS inhibitor) or aminoguanidine (a selective iNOS inhibitor) was given p.o. twice daily for 6 days starting from the termination of DSS treatment. The area of lesions, colon length and MPO activity were measured on day 7 after DSS treatment. DSS treatment caused severe lesions in the colon, accompanied by an increase in MPO activity and a decrease in colon length. The lesions healed gradually after discontinuation of DSS treatment, with a histological restoration and subsidence of inflammation. The healing of DSS-induced colonic lesions was significantly impaired by daily administration of L-NAME or aminoguanidine, the effects being all but equivalent between these drugs, and the effect of L-NAME was significantly reverted by the co-administration of L-arginine. The expression of nNOS protein was observed in the colonic mucosa with or without DSS treatment, while those of iNOS and eNOS were markedly upregulated after DSS treatment. Likewise, the expression of VEGF was also up-regulated in the colon following DSS treatment, and this response was suppressed by both L-NAME and aminoguanidine. These results suggest that endogenous NO produced by mainly iNOS and partly eNOS contributes to the healing of DSS-induced colonic lesions, through the upregulation of VEGF expression and enhancement of angiogenesis.

19

Ulcerogenic and healing impairing actions of monochloramine in rat stomachs: effects of zinc L-carnosine, polaprezinc

38%

Nishiwaki H. , Kato S. , Sugamoto S. , Umeda M. , Morita H. , Yoneta T. , Takeuchi K.

Journal of Physiology and Pharmacology

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1999

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tom 50

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nr 2

20

Prevention by lansoprazole, a proton pump inhibitor, of indomethacin-induced small intestinal ulceration in rats through induction of heme oxygenase-1

32%

Yoda Y. , Amagase K. , Kato S. , Tokioka S. , Murano M. , Kakimoto K. , Nishio H. , Umegaki E. , Takeuchi K. , Higuchi K.

Journal of Physiology and Pharmacology

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2010

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tom 61

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nr 3

287-294

EN

The effect of lansoprazole, a proton pump inhibitor (PPI), on indomethacin-induced small intestinal ulceration was examined in rats, particularly in relation to heme oxygenase (HO)-1. The animals were administered indomethacin (10 mg/kg, p.o.) and killed 24 h later. Lansoprazole (30-100 mg/kg, p.o.) and omeprazole (30-100 mg/kg, p.o.) were given 30 min before the administration of indomethacin, while tin-protoporphyrin IX (SnPP: 30 mg/kg, i.v.), an inhibitor of HO-1, was injected 10 min before indomethacin or lansoprazole. Indomethacin produced hemorrhagic lesions in the small intestine, accompanied with an increase of mucosal invasion of enterobacteria, inducible nitric oxide synthase (iNOS) expression, and myeloperoxidase (MPO) activity in the mucosa. Pretreatment with lansoprazole dose- dependently reduced the severity of the indomethacin-induced intestinal lesions, with suppression of the increased MPO activity, while omeprazole had no effect. Pretreatment with SnPP significantly exacerbated these intestinal lesions and almost totally abolished the protective effect of lansoprazole. The up-regulation of iNOS mRNA expression following indomethacin was suppressed by lansoprazole in a SnPP-inhibitable manner, although the enhanced enterobacterial invasion remained unaffected. The amount of HO-1 protein in the intestinal mucosa was significantly increased by lansoprazole but not by omeprazole. Prior administration of carbon monoxide (CO)-releasing molecule-2 (CORM-2; 10 mg/kg, i.p.) significantly reduced the severity of these lesions and the enhancement of mucosal iNOS mRNA expression induced in the small intestine by indomethacin. These results suggest that lansoprazole prevents indomethacin-induced small intestinal ulceration, and this effect is associated with inhibition of iNOS expression, through up-regulation of HO-1/CO production in the mucosa.