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1

The effect of antagonist of receptors for gastrin, cholecystokinin and bombesin on growth of gastroduodenal mucosa and pancreas

100%

Dembinski A. , Warzecha Z. , Konturek S. J. , Banas M. , Cai R.-Z. , Schally A. V.

Journal of Physiology and Pharmacology

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1991

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tom 42

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nr 3

EN

The effects of gastrin, cholecystokinin (CCK) and bombesin on the DNA synthesis, as a biochemical indicator of trophic action in the gastroduodenal mucosa and the pancreas, have been examined in rats fasted for 48 h and in rats refed for 16 h with or without administration of specific receptor antagonists for bombesin, gastrin and CCK. Bombesin and gastrin administered three times daily for 48 h in fasted rats significantly increased the rate of DNA synthesis as measured by the incorporation of [³H] thymidine into DNA in each tissue tested. CCK significantly increased DNA synthesis in the duodenal mucosa and pancreatic tissue, but not in the gastric mucosa. The stimulation of DNA synthesis induced by bombesin in the gastroduodenal mucosa and pancreas was abolished by bombesin/GRP receptor antagonist, RC-3095. RC-3095 did not affect DNA synthesis stimulated by gastrin and CCK in these tissues. L-365,260, a receptor antagonist for gastrin suppressed the DNA synthesis induced by gastrin but not by CCK or bombesin in the gastrointestinal mucosa and pancreas. L-364,718, a specific antagonist for CCK receptors was effective only against CCK stimulated duodenal mucosa and pancreatic growth. Refeeding of 48 h fasting rats strongly enhanced the DNA synthesis in all tissues tested, and this effect was significantly reduced in the gastroduodenal mucosa by blocking only gastrin receptors (with L-365, 260) and that in the duodenal mucosa and the pancreas by antagonizing of CCK receptors (with L-364, 718). Antagonism of bombesin receptors (with RC-3095) did not significantly affect the stimulation of DNA synthesis induced by refeeding in all tissues tested. This study indicates that the stimulation of DNA synthesis can be achieved by exogenous gastrin, CCK and bombesin acting through separate receptors, but that only gastrin and CCK play the major role in the postprandial stimulation of the growth of gastroduodenal mucosa and pancreatic tissue.

2

Influence of Viburnum opulus proanthocyanidins on stress-induced gastrointestinal mucosal damage

84%

Zayachkivska O. S. , Gzhegotsky M. R. , Terletska O. I. , Lutsyk D. A. , Yaschenko A. M. , Dzhura O. R.

Journal of Physiology and Pharmacology. Supplement

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2006

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tom 57

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nr 5

155-167

EN

Recent studies demonstrated that the proanthocyanidins (PA), the polymers of flavan-3-ols, naturally occurring plant metabolites widely available in fruits, vegetables, nuts, seeds, flowers and bark, have anti-inflammatory, anticarcinogenic, anti-allergic, antioxidant and vasodilatory actions. We hypothesized that Viburnum opulus PA (VOPA, Caprifoliaceae), due to activation of multifactorial gastrointestinal mucosal defense mechanisms, exert gastroduodenoprotective effects. The aim of the study was: 1) to investigate VOPA effects on gastroduodenal mucosal integrity and pattern of carbohydrate binding proteins and nitric oxide (NO) content in intact mucosa and that exposed to non-topical ulcerogens (stress) in rats without and with capsaicin (125 mg/kg, sc) denervation; and 2), to assess the role of activity of antioxidizing enzymes superoxide dismutase (SOD), catalase (CAT), gluthatione peroxidase (GPx) in VOPA-iduced gastroduodenoprotection against water immersion and restraint stress (WRS) in rats. VOPA was administered orally in dose of 25, 50 or 75 mg/kg body weight. Gastroduodenal mucosal damage detected by routine light microscopic investigation and lectin histochemistry set, purified from plant and animal sources of Carpatian region. NO content, pro-and antioxidant system were determinated by routine laboratory methods. Pretreatment with VOPA afforded gastroduodenoprotection and was accompanied by an increase in NO expression, both changes being reversed by sensory denervation, as well as by the rise of SOD, CAT activity and fall in MDA content. Our study shows that VOPA exerts a potent gastroduodenoprotective activity via an increase in endogenous NO generation, suppression of lipid peroxidation and mobilization of antioxidant activity and changes in glycoconjugate content of the gastroduodenal mucosa of rat.

3

The effects of antagonists of receptors for gastrin, cholecystokinin and bombesin on growth of gastroduodenal mucosa and pancreas

84%

Dembinski A. , Warzecha Z. , Konturek S. J. , Zhi Cai R. , Schally A. V.

Journal of Physiology and Pharmacology

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1991

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tom 42

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nr 2

EN

The effects of gastrin, cholecystojdnin (CCK) and bombesin on the DNA synthesis, as a biochemical indicator of trophic action in the gastroduodenal mucosa and the pancreas have been examined in rats fasted for 48 h and in rats refed for 16 h with or without administration of specific receptor antagonists for bombesin, gastrin and CCK. Bombesin and gastrin administered three times daily for 48 h in fasted rats significantly increased the rate of DNA synthesis as measured by the incorporation of [³H] thymidine into DNA in each tissue tested. CCK significantly increased DNA synthesis in the duodenal mucosa and pancreatic tissue, but not in the gastric mucosa. The stimulation of DNA synthesis induced by bombesin in the gastroduodenal mucosa and pancreas was abolished by bombesin/GRP receptor antagonist, RC-3095. RC-3095 did not affect DNA synthesis stimulated by gastrin and CCK in these tissues. L-365,260, a receptor antagonist for gastrin suppressed the DNA synthesis induced by gastrin but not by CCK or bombesin in the gastrointestinal mucosa and pancreas. L-364, 718 a specific antagonist for CCK receptors was effective only against CCK stimulated duodenal mucosa and pancreatic growth. Refeeding of 48 h fasting rats strongly enhanced the DNA synthesis in all tissues tested, and this effect was significantly reduced in the gastroduodenal mucosa by blocking only gastrin receptors (with L-365, 260) and that in the duodenal mucosa and the pancreas by antagonizing of CCK receptors (with L-364, 718). Antagonism of bombesin receptors (with RC-3095) did not significantly affect the stimulation of DNA synthesis induced by refeeding in all tissues tested. This study indicates that the stimulation of DNA synthesis can be achieved by exogenous gastrin, CCK and bombesin acting through separate receptor but that only gastrin and CCK play the major role in the postprandial stimulation of the growth of gastroduodenal mucosa and pancreatic tissue.

4

Influence of ghrelin on gastric and duodenal growth and expression of digestive enzymes in young mature rats

84%

Warzecha Z. , Dembinski A. , Ceranowicz P. , Dembinski M. , Cieszkowski J. , Konturek S. J. , Polus A. , Pawlik W. W. , Kuwahara A. , Kato I. , Konturek P. C.

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nr 3

EN

Ghrelin, a nature ligand for the growth hormone secretagogue receptor (GHS-R), stimulates a release of growth hormone, prolactin and adrenocorticotropic hormone. Also, ghrelin increases food intake in adult rats and humans and exhibits gastroprotective effect against experimental ulcers induced by ethanol or stress. The aim of present study was to examine the influence of ghrelin administration on gastric and duodenal growth and expression of pepsin and enterokinase in young mature rats with intact or removed pituitary. Methods: Two week after sham operation or hypophysectomy, eight week old Wistar male rats were treated with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose) i.p. twice a day for 4 days. Expression of pepsin in the stomach and enterokinase in the duodenum was evaluated by real-time PCR. Results: In animals with intact pituitary, treatment with ghrelin increased food intake, body weight gain and serum level of growth hormone and insulin-like growth factor-1 (IGF-1). These effects were accompanied with stimulation of gastric and duodenal growth. It was recognized as the significant increase in gastric and duodenal weight and mucosal DNA synthesis. In both organs, ghrelin administered at the dose of 8 nmol/kg caused maximal growth-promoting effect. In contrast to these growth-promoting effects, administration of ghrelin reduced expression of mRNA for pepsin in the stomach and was without effect on expression of mRNA for enterokinase in the duodenum. Hypophysectomy alone lowered serum concentration of growth hormone under the detection limit and reduced serum level of IGF-1 by 90%. These effects were associated with reduction in daily food intake, body weight gain and gastroduodenal growth. In hypophysectomized rats, administration of ghrelin was without significant effect on food intake, body weight gain or growth of gastroduodenal mucosa. Also, serum concentration of growth hormone or IGF-1 was not affected by ghrelin administration in rats with removed pituitary. Conclusion: Administration of ghrelin stimulates gastric and duodenal growth in young mature rats with intact pituitary, but inhibits expression of mRNA for pepsin in the stomach. Growth hormone and insulin-like growth factor-1 play an essential role in growth-promoting effects of ghrelin in the stomach and duodenum.

5

Prostaglandin E receptor subtypes involved in stimulation of gastroduodenal bicarbonate secretion in rats and mice

84%

Takeuchi K. , Ukawa H. , Furukawa O. , Kawauchi S. , Araki H. , Sugimoto Y. , Ishikawa A. , Ushikubi F. , Narumiya S.

Journal of Physiology and Pharmacology

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1999

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tom 50

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nr 2

6

The role of female and male sex hormones in the healing process of preexisting lingual and gastric ulcerations

67%

Machowska A. , Szlachcic A. , Pawlik M. , Brzozowski T. , Konturek S. J. , Pawlik W. W.

Journal of Physiology and Pharmacology. Supplement

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2004

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tom 55

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nr 2

91-104

EN

Studies in different animal species and in humans have suggested that sex hormones influence gastric acid secretion and contribute to the integrity of the oral and gastroduodenal mucosa but the effect of male and female sex hormones on the healing of the preexisting ulcers in the oral cavity and stomach have not been studied. We compared the effects of major male hormone, testosterone, and female hormone, progesterone, on the healing of lingual and gastric ulcers induced by acetic acid technique in male rats with intact or removed testicles (testectomy) and female rats with intact or removed ovaries (ovariectomy). The gastric acid secretion was determined in rats with gastric ulcers equipped with chronic gastric fistula (GF). Rats were sacrificed at day 7 upon ulcer induction; the ulcer area was measured by planimetry and the lingual and gastric blood flow (GBF) was determined by H2-gas clearance method and venous blood was collected for determination of plasma gastrin and plasma proinflammatory cytokine interleukin (IL)-1ß levels. Gastric acid output from GF rats was significantly reduced while plasma gastrin was significantly enhanced in testectomized animals as compared to those in intact control rats and these effects were reversed by supplementation of testectomized animals with testosterone. The area of lingual and gastric ulcers in placebo-control rats decreased significantly at day 7 and this effect was significantly accelerated by testectomy or ovariectomy. In contrast, testosterone significantly delayed ulcer healing while producing a significant fall in the gastric blood flow and lingual blood flow determined at the margin of these ulcers. Treatment with progesterone significantly accelerated ulcer healing and increased the gastric and lingual blood flow at margin of these ulcers. Testosterone applied alone or supplemented in testectomized animals produced the significant increment in plasma IL-1ß levels as compared to the respective levels of this cytokine in placebo-control animals. We conclude that: 1) major male (testosterone) and female (progesterone) sex hormones exhibit opposite effect on healing of preexisting ulcers in the oral cavity and stomach because testosterone markedly delayed while progesterone significantly accelerated this healing; 2) testosterone-induced delay in ulcer healing involves the fall in the gastric microcirculation at the margin of lingual and gastric ulcers and the excessive production and release of proinflammatory cytokine IL-1ß; and 3) testectomy improves the gastric ulcer healing due to inhibition of gastric acid secretion and the rise in plasma gastrin, which exerts gastroprotective, trophic and ulcer healing action on the gastric mucosa.

7

Adaptation of gastric mucosa to stress. Effect of ranitidine

59%

Ernst H. , Konturek P. C. , Brzozowski T. , Lochs H. , Hahn E. G. , Konturek S. J.

Journal of Physiology and Pharmacology

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1998

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tom 49

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nr 3