Koji Takeuchi

Koji Takeuchi
Kyoto Pharmaceutical University · Pharmacology and Experimental Therapeutics

About

830
Publications
24,994
Reads
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16,370
Citations
Citations since 2016
3 Research Items
3114 Citations
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
Additional affiliations
April 1995 - March 2013
Kyoto Pharmaceutical University
Position
  • Professor Emeritus

Publications

Publications (830)
Article
Background: We introduced a rat model of ischemic enteritis and investigated the roles of enterobacteria, nitric oxide (NO), and prostaglandins (PGs) in its pathogenesis. Methods: Male rats were used after 18 h of fasting. Ischemic enteritis was induced by partial ligation of the superior mesenteric artery (SMA). Under ether anesthesia, SMA was...
Article
Full-text available
Background/Aim: Muscarinic acetylcholine receptors exist in five subtypes (M1∼M5), and they are widely expressed in various tissues to mediate diverse autonomic functions, including gastric secretion. In the present study, we demonstrated, using M1∼M5 KO mice, the importance of M4 receptors in carbachol (CCh) stimulation of acid secretion and inves...
Article
Full-text available
We examined the influence of adrenalectomy on NSAID-induced small intestinal damage in rats and investigated the possible involvement of adrenal glucocorticoids in the protective effects of urocortin I, a corticotropin-releasing factor (CRF) agonist. Male SD rats without fasting were administered indomethacin s.c. and killed 24 h later in order to...
Article
Full-text available
Monosodium glutamate (MSG) is known to provide the umami taste in the food. We have recently reported that glutamate has the potential to protect the small intestine against non-steroidal anti-inflammatory drugs (NSAIDs)-induced lesions in rats. In this paper, we examined this protective effect using sodium loxoprofen, one of the NSAIDs frequently...
Article
We investigated the roles of muscarinic (M) acetylcholine receptor subtype in the cholinergic stimulation of duodenal HCO3(-) secretion using knockout (KO) mice. Wild-type and M1-M5 KO C57BL/6J mice were used. The duodenal mucosa was mounted on an Ussing chamber, and HCO3(-) secretion was measured at pH 7.0 using a pH-stat method in vitro. Carbacho...
Article
We herein reviewed the mechanism underlying the gastric hyperemic response following barrier disruption, with a focus on cyclooxygenase (COX) isozymes, prostaglandin (PG) E2, and capsaicin-sensitive afferent neurons. Mucosal damage was induced by exposing the stomach to 20 mM taurocholate (TC) with 50 mM HCl. The TC treatment disrupted surface epit...
Article
NSAID-induced enteropathy has been the focus of recent basic and clinical research subsequent to the development of the capsule endoscope and double-balloon endoscope. We review the possible pathogenic mechanisms underlying NSAID-induced enteropathy and discuss the role of the inhibition of COX-1/COX-2 and the influences of food as well as various...
Article
Prostaglandin E2 not only prevents NSAID-generated small intestinal lesions, but also promotes their healing. The protective effects of prostaglandin E2 are mediated by the activation of EP4 receptors and functionally associated with the stimulation of mucus/fluid secretions and inhibition of intestinal hypermotility, resulting in the suppression o...
Article
We investigated the roles of cyclooxygenase (COX) isozymes and prostaglandins (PGs) and their receptors in mucosal defense against cold-restraint stress (CRS)-induced gastric lesions. Male C57BL/6 wild-type (WT) mice and those lacking COX-1 or COX-2 as well as those lacking EP1, EP3, or IP receptors were used after 18 h fasting. Animals were restra...
Article
We examined the prophylactic effect of rebamipide on gastric bleeding induced by the perfusion of aspirin (acetylsalicylic acid [ASA]) plus clopidogrel under the stimulation of acid secretion in rats. Under urethane anesthesia, acid secretion was stimulated by the i.v. infusion of histamine (8 mg/kg/h), and the stomach was perfused with 25 mmol/L A...
Article
Hydrogen sulfide (H2S) is known to be an important gaseous mediator that affects various functions under physiological and pathological conditions. We examined the effects of NaHS, a H2S donor, on HCO3(-) secretion in rat stomachs and investigated the mechanism involved in this response. Under urethane anesthesia, rat stomachs were mounted on an ex...
Article
Aims: The present study compared the effects of frequently used anti-platelet drugs, such as clopidogrel, ticlopidine, and cilostazol, on the gastric bleeding and ulcerogenic responses induced by intraluminal perfusion with 25 mM aspirin acidified with 25 mM HCl (acidified ASA) in rats. Main methods: The stomach was perfused with acidified ASA at a...
Article
Aims: The present study compared the effects of frequently used anti-platelet drugs, such as clopidogrel, ticlopidine, and cilostazol, on the gastric bleeding and ulcerogenic responses induced by intraluminal perfusion with 25 mM aspirin acidified with 25 mM HCl (acidified ASA) in rats. Main methods: The stomach was perfused with acidified ASA a...
Conference Paper
We examined the effect of H2S on duodenal HCO3- secretion in rats and investigated the mechanism involved in this response. Animals were fasted overnight and anesthetized with urethane. A duodenal loop was perfused with saline, and HCO3- secretion was measured at pH 7.0 using a pH stat-method. The loop was perfused at a rate of 0.2 mL/min with NaHS...
Article
Lubiprostone, a bicyclic fatty acid derived from prostaglandin E1, has been used to treat chronic constipation and irritable bowel syndrome, and its mechanism of action has been attributed to the stimulation of intestinal fluid secretion via the activation of ClC-2/CFTR chloride channels. We examined the effects of lubiprostone on indomethacin-indu...
Article
Full-text available
Esophagitis was induced in rats within 3 h by ligating both the pylorus and transitional region between the forestomach and glandular portion under ether anesthesia. This esophageal injury was prevented by the administration of acid suppressants and antipepsin drug and aggravated by exogenous pepsin. Damage was also aggravated by pretreatment with...
Article
Endogenous prostaglandins (PGs) play a role in modulating mucosal integrity and have various functions in the stomach, with E type PGs being the most effective. PGE2 provides gastric cytoprotection against damage induced in rats by HCl/ethanol, indomethacin, or acid back-diffusion after barrier disruption. These effects were mimicked by EP1 agonist...
Article
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications worldwide, but cause damage in the small intestine as well as stomach. Probiotic preparations, especially containing live lactic acid bacteria, have been used for treatment of bowel disturbances such as diarrhea and constipation. In the present study,...
Article
Full-text available
Antisecretory drugs such as histamine H2-receptor antagonists and proton pump inhibitors are commonly used for the treatment of upper gastrointestinal mucosal lesions induced by NSAIDs. However, it has recently been reported that these drugs exacerbate NSAID-induced small intestinal lesions in rats. Unfortunately, there are few effective agents for...
Article
Full-text available
High-mobility group box 1 (HMGB1) was initially discovered as a nuclear protein that interacts with DNA as a chromatin-associated non-histone protein to stabilize nucleosomes and to regulate the transcription of many genes in the nucleus. Once leaked or actively secreted into the extracellular environment, HMGB1 activates inflammatory pathways by s...
Article
The extracellular calcium-sensing receptor (CaSR), a G protein-coupled cell receptor cloned from bovine parathyroid, has been demonstrated to play a regulatory role in various functions of the gastrointestinal tract. In the present study, we examined the effect of cinacalcet, a drug that acts as a calcimimetic through the allosteric activation of C...
Article
We examined changes in the expression of a pro-angiogenic factor, vascular endothelial growth factor (VEGF), and an anti-angiogenic factor, endostatin, as well as matrix metalloproteinase (MMP)-2 and MMP-9 in the rat small intestine after administration of indomethacin and investigated the roles of these factors in the healing of indomethacin- indu...
Article
We reviewed the prophylactic effect of monosodium glutamate (MSG), a substance known as the "umami", on NSAID-induced small intestinal damage in rats. Loxoprofen, one of NSAIDs frequently used in Asian countries, given orally at 60 mg/kg, caused hemorrhagic damage in the small intestine, mainly jejunum and ileum, concomitant with a down-regulation...
Article
Background/aims: The effects of feeding conditions (fasted or fed) and dietary fiber (DF) in the diet on gastrointestinal (GI) damage induced by aspirin (ASA) were examined in cats. Methods: Plain ASA (P-ASA, 20 mg/kg) or one enteric-coated ASA tablet (EC-ASA, containing 100 mg ASA) was administered p.o. once daily for 3 or 7 days just after mor...
Article
We set up two models of gastric bleeding in rats using low-dose aspirin (ASA) and the antiplatelet drug clopidogrel, a P2Y12 receptor antagonist, and examined the effect of antiulcer drugs on gastric bleeding and ulcerogenic responses under such conditions. Under urethane anesthesia, two catheters were inserted into the rat stomach, one from the es...
Article
Full-text available
Atrophic gastritis caused by infection with Helicobacter pylori is characterized by parietal cell loss, which is a main risk factor for gastric cancer. Parietal cells play a crucial role in the regulation of cell lineage maturation and proliferation in the gastric units. Among the classical cadherins, E-cadherin plays an important role not only in...
Article
Enterobacteria play important roles in the pathophysiology of small intestinal injuries induced by nonsteroidal anti-inflammatory drugs (NSAIDs). We investigated the effects of rebamipide, a gastrointestinal mucoprotective drug, on indomethacin-induced small intestinal injuries, intestinal microbiota, and expression levels of α-defensin 5, which is...
Article
We examined the effect of egualen, a stable azulene derivative, against gastric damage induced by ischemia/reperfusion (I/R), gastric bleeding induced by double antiplatelet therapy with aspirin (ASA) plus clopidogrel, and small intestinal damage generated by loxoprofen, and investigated the possible mechanisms involved in its protective action. Ma...
Article
Background and purpose: Chemotherapeutic agents, including 5-fluorouracil (5-FU), frequently cause intestinal mucositis resulting in severe diarrhoea and morphological mucosal damage. 5-HT₃ receptor antagonists are clinically effective in the treatment of nausea and emesis during cancer chemotherapy. Therefore we here have examined the effects of...
Article
Full-text available
Background and Aim. New diagnostic or therapeutic methods in endoscopy have been used. Current clinical application of these procedures is not well known. The aim of this study is to investigate the present situation on endoscopic diagnosis and treatment of gastrointestinal disorders in East Asian countries. Method. A representative member from the...
Article
We previously proposed that direct cytotoxicity of NSAIDs due to their membrane permeabilization activity, together with their ability to decrease gastric prostaglandin E(2), contributes to production of gastric lesions. Compared to loxoprofen (LOX), fluoro-loxoprofen (F-LOX) has much lower membrane permeabilization and gastric ulcerogenic activiti...
Article
Full-text available
Though NSAIDs often cause ulcers in the duodenum in humans, the role of cyclooxygenase (COX) isoforms in the pathogenesis of duodenal ulcers has not been fully elucidated. We examined in cats the (1) ulcerogenic effects of selective COX-1 (SC-560, ketorolac) and COX-2 (celecoxib, meloxicam) inhibitors on the gastrointestinal mucosa, (2) effect of f...
Article
Irsogladine, a mucosal protective drug, was developed in Japan for the treatment of peptic ulcer disease and acute gastritis. This drug is superior to gefarnate, the same therapeutic category drug, in a randomized, controlled and double-blind clinical study in 1987. The mechanisms of irsogladine's actions are apparently different from those of anti...
Article
Full-text available
Antisecretory drugs such as histamine H(2)-receptor antagonists (H(2)-RAs) and proton pump inhibitors (PPIs) are commonly used for the treatment of gastric and duodenal ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs). However, the effects of these drugs on NSAID-induced small intestinal ulcers are not fully understood. The effects o...
Article
Bisphosphonates (BPPs) were developed as antiresorptive drugs capable of treating diseases related to bone remodeling; however, they have untoward effects including ulceration in the upper gastrointestinal tract and worsen the healing-impairment action of nonsteroidal anti-inflammatory drugs, prescribed in patients with arthritis or osteoporosis. W...
Article
Serotonin (5-HT) exerts multiple physiological functions not only in the central and peripheral nervous systems but also in the gastrointestinal tract, and these multiple functions are accounted for by a variety of 5-HT receptor subtypes. We investigated the role of 5-HT in the pathogenesis of indomethacin-induced intestinal lesions in mice, in rel...
Article
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, decrease mucosal prostaglandin (PG) E 2 content by inhibiting cyclooxygenase (COX) activity and cause damage in the small intestine. The development of these lesions required the inhibition of both COX-1 and COX-2, because inhibition of COX-1 up-regulated COX-2 expression and PGs...
Article
This article is the review of the recent reports in which a chronic gastric ulcer model, so-called acetic acid ulcer, was used during 2010-2012. Thirteen new papers were published to elucidate the mechanism of ulcer healing using rats and mice. In addition, 11 substances, mainly extracted from plants used for folk medicine and a proton pump inhibit...
Article
In humans, nonsteroidal anti-inflammatory drugs (NSAIDs) cause mucosal damage in the small intestine as well as in the stomach and duodenum. Gastric and duodenal lesions caused by NSAIDs can be effectively treated with antisecretory agents; however, there are few effective agents for the treatment of small intestinal lesions. Therefore, development...
Article
Although antithrombotic therapy plays a central role in the treatment of cardiac disorders and peripheral arterial diseases, recent studies suggest that the risk of upper gastrointestinal bleeding is increased by the concomitant use of anti-platelet drugs with low-dose aspirin. We set up a screening model of gastric bleeding in rats using low-dose...
Article
Full-text available
Toll-like receptors (TLRs) recognize microbial components and trigger the signaling cascade that activates innate and adaptive immunity. Recent studies have shown that the activation of TLR-dependent signaling pathways plays important roles in the pathogenesis of ischemia-reperfusion (I/R) injuries in many organs. All TLRs, except TLR3, use a commo...
Article
Background/Aim: Helicobacter pylori (H. pylori), recognized as the major cause of gastritis and peptic ulcer diseases, has a high activity of urease, resulting in an abnormally high concentration of ammonia (NH 4+) in the stomach of infected patients. In the present study, we investigated whether HYAKUSOGAN, a gastroprotective drug which is a combi...
Article
This article reviews the pathogenic mechanism of non-steroidal anti-inflammatory drug (NSAID)-induced gastric damage, focusing on the relation between cyclooxygenase (COX) inhibition and various functional events. NSAIDs, such as indomethacin, at a dose that inhibits prostaglandin (PG) production, enhance gastric motility, resulting in an increase...