Biomedical subjects

Susumu Okabe

Publications and source records attributed to Susumu Okabe.

24 records · Page 2Linked to original sources

PubMed2003

[New target for the inhibitors of gastric acid secretion. Inhibition of myosin and actin activities via the apical membrane of parietal cells in dogs].

This report aims to highlight drugs that are able to inhibit parietal cells from the luminal side, resulting in suppressed gastric acid secretion. Histamine 2HCl was i.v. given continuously to obtain a submaximal stimulation of gastric acid secretion. Wortmannin and ME 3407 (a myosin light chain kinase inhibitor) and cytocharasin D (actin polymerizing inhibitor) were locally applied to denervated gastric pouches prepared in dogs for 5 to 30 min. Each drug, administered 0.5 hr before or 1 hr after histamine infusion was commenced, significantly inhibited stimulated-gastric acid secretion in a time-dependent manner. The antisecretory effect persisted for more than 24 hrs in the case of Wortmannin and 9 hr in the case of ME 3407 at a dosage 1 and 3 mg/pouch for 30 min, respectively. ME 2407, however, had no antisecretory effect when i.v. administered after histamine infusion, or orally administered before histamine infusion. Such results strongly suggest that the apical membrane of parietal cells possesses a ME 4307, Wortmannin and cytocharasin D sensitive portion similar to the basolateral membrane that usually mediates gastric acid secretion. The apical membrane represents an intriguing target for developing new antisecretory drugs, as well as for elucidating the functional features of parietal cells.

Actins↗

PubMed2002

Chitosan capsules for colon-specific drug delivery: enhanced localization of 5-aminosalicylic acid in the large intestine accelerates healing of TNBS-induced colitis in rats.

The objective of this study was to achieve the colon-specific delivery of an anti-ulcerative colitis drug using chitosan capsules and to accelerate healing of 2,4,6-trinitrobenzene sulfonic acid sodium salt (TNBS)-induced colitis in rats. 5-Aminosalicylic acid (5-ASA) was used as a model of an anti-inflammatory drug. The gastrointestinal transit of chitosan capsules was determined by counting the number of capsules in the gastrointestinal lumen by celiotomy at certain times after their oral administration to rats. The chitosan capsules reached the large intestine 3.5 h after oral administration in rats. We studied the release of 5-ASA from chitosan capsule by the Japan Pharmacopoeia (JP) rotating basket method. The release of 5-ASA from the chitosan capsule markedly increased in the presence of rat cecal contents. After oral administration of chitosan capsules containing 5-ASA, the concentrations of 5-ASA in the large intestinal mucosa were higher than those in the CMC suspension. For the treatment of colitis in rats, 5-ASA was orally administered using chitosan capsules or a carboxy methyl cellulose (CMC) suspension to TNBS-induced rats. The colonic injury and inflammation were assessed by measuring the myeloperoxidase (MPO) activities, colon wet weight/body weight (C/B) ratio and the damage score, respectively. When 5-ASA was orally administered using chitosan capsules in TNBS-induced colitis rats, we found better therapeutic effects with 5-ASA than with a 5-ASA CMC suspension, as evaluated by the MPO activities, C/B ratio and the damage score. In conclusion, chitosan capsules may be useful carriers for the colon-specific delivery of anti-inflammatory drugs including 5-ASA and the healing of TNBS-induced colitis in rats.

Administration, Oral↗

PubMed2002

Influence of Helicobacter pylori infection on healing and relapse of acetic acid ulcers in Mongolian gerbils.

Both Helicobacter pylori and NSAIDs play important roles in the healing and relapse of peptic ulcers in man. We examined how H. pylori infection, indomethacin, and their combination affects the healing of gastric ulcers and whether or not such factors provoke a relapse of healed gastric ulcers in Mongolian gerbils. Gastric ulcers were induced by serosal application of an acetic acid solution. H. pylori (ATCC43504) was orally administered once into animals with active and healed ulcers. Ulcers healed within eight weeks and remained healed for the following six months. H. pylori infection significantly delayed ulcer healing four weeks following infection. Indomethacin treatment showed a tendency to delay ulcer healing. Ulcer healing in H. pylori-infected Mongolian gerbils was significantly delayed by indomethacin. H. pylori infection resulted in a relapse of healed ulcers from one to six months after infection, with a gradual increase in size. By the fourth month following a relapse, the serum gastrin level had significantly increased. H. pylori-induced ulcers in the posterior wall coexisted with relapsed ulcers in the anterior wall five and six months later. Omeprazole markedly prevented the ulcer relapse caused by H. pylori infection. It is concluded that, in Mongolian gerbils, H. pylori infection delayed the healing of preexisting gastric ulcers and resulted in the relapse of healed ulcers, yet indomethacin had little or no effect on ulcer healing or relapse.

Acetic Acid↗

PubMed2002

Gastric acid secretion in L-histidine decarboxylase-deficient mice.

BACKGROUND & AIMS: Histamine, gastrin, and acetylcholine are known to be the primary secretagogues of gastric acid secretion, but how the roles are shared among these secretagogues remains to be fully clarified. To evaluate the cooperation between histamine and the other secretagogues, acid secretion responses induced by each secretagogue were measured in L-histidine decarboxylase (HDC)-deficient mice. METHODS: Acid secretion was measured by the titration of acid under anesthesia. The expression of selected genes involved in acid secretion was determined by Northern blot and/or immunoblot analysis. Histamine-2 (H(2)) receptor binding in the gastric mucosa was investigated using [(3)H]tiotidine. RESULTS: HDC-deficient mice showed low basal and high exogenous histamine-stimulated acid secretion. The mutant mice showed hypergastrinemia and did not undergo acid secretion upon treatment with exogenous gastrin. However, carbachol stimulated weak and transient acid secretion in the mutants. The Bmax values for H(2) and the expression of Gs alpha in gastric mucosal membranes were higher in the mutants than in the wild-type mice. CONCLUSIONS: This study confirms the concept that histamine production is essential for gastric acid secretion induced by gastrin, but not for that induced by carbachol. HDC-deficient mice should be a suitable model for further functional analyses of the correlation between histamine and the other acid secretagogues.

Animals↗

PubMed2002

Effect of rebamipide on cell death induced by combined treatment of mild heat shock and quercetin in RGM-1 cells: a role for HSP70 induction.

The mechanism by which rebamipide inhibits cell death induced by combined treatment of mild heat shock and quercetin in RGM-1 cells was examined. Cells were incubated at 42 degrees C for 1 h with or without quercetin. Expression of HSP70 was detected by immunoblot analysis and cell viability was determined by the MTT method. Upon treatment of cells with heat shock in the presence of quercetin, cell viability was significantly decreased 24 h after heat shock, with strong inhibition of HSP70 expression. Rebamipide suppressed both cell death and a reduction in HSP70 induced by the combined treatment of heat shock and quercetin. The combination of heat shock and quercetin resulted in DNA fragmentation, but rebamipide managed to inhibit such fragmentation. The protective effect of rebamipide was eliminated by cycloheximide or actinomycin D. Based upon these findings, it was concluded that rebamipide inhibited cell death resulting from combined treatment of mild heat shock and quercetin. The protective action of rebamipide appears to be at least partially due to maintenance of the HSP70 level.

Alanine↗

PubMed2002

[Regulatory mechanism of gastric acid secretion and mucosal integrity--an analysis with various gene deficient mice].

UNLABELLED: Mechanisms for gastric acid secretion have been elucidated through invention of new methods and new drugs. Current genetic technology have generated knockout (KO) mice lacking receptors such as CCK2, histamine H2, muscarinic M3 and M1, or enzymes such as histidine decarboxylase (HDC) and H+,K(+)-ATPase. Here, we review the functional and morphological changes in the gastric mucosa of such KO mice. In M3R-KO mice (intragastric pH 5.9), carbachol, histamine and gastrin stimulated acid secretion like they did in wild-type mice. Carbachol-stimulated acid secretion was significantly inhibited by famotidine and pirenzepine. The serum gastrin level in M3R-KO mice was increased, yet the stomach weight and the gastric mucosa remained unchanged. In H2R-KO mice (intragastric pH 3.0), serum gastrin and mucosal histamine levels significantly increased. Carbachol significantly stimulated acid secretion, yet histamine and gastrin had little or no effect on acid secretion. The stomach wet weight increased with time after birth and the serum albumin level was decreased. In the gastric mucosa with hyperplasia, numerous enlarged cysts and a marked expression of TGF-alpha were observed, indicating the occurrence of Menetrier's disease like mucosal changes. G/D cell ratio was greatly increased, providing evidence of the increased serum gastrin level. In HDC-KO mice (intragastric pH 4.5), the stomach weight was also increased 6 mo after birth, with no enlarged cysts in the gastric mucosa. CONCLUSION: The above results indicate that KO mice can be used to yield many important findings that selective antagonists cannot reveal.

Animals↗