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Physiological, immunohistochemical and molecular aspects of gastric adaptation to stress, aspirin and to H.pylori - derived gastrotoxins

100%

Konturek P. C.

Journal of Physiology and Pharmacology

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1997

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tom 48

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nr 1

2

The history of gastrointestinal hormones and the Polish contribution to elucidation of their biology and relation to nervous system

64%

Konturek P. C., Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

|

2003

|

tom 54

|

nr 3

83-98

At the turn of XIX and XX century, the principal concept explaining the mechanism of secretory activity of the digestive glands was nervism proposed by I. P. Pavlov at Russian physiological school in St Petersburg, and this dogma was widely recognized for several years in other countries. The discovery of secretin in 1902 by W.B. Bayliss and E.H. Starling, and then of gastrin in 1906 by J.S. Edkins, emphasized the hormonal regulation of pancreatic and gastric secretion, respectively. In 1943, A.C. Ivy and E. Olberg discovered a hormone, which contracts the gallbladder - cholecystokinin (CCK), while A. Harper and H.S. Raper described another hormone, pancreozymin, which stimulated pancreatic enzymes. It required over twenty years, however, for these and many other hormones to be identified, purified and synthesized due to the extensive work of several teams including R. Gregory, G. Dockray and Kenner of the UK; J. Rehfeld of Denmark and E. Wunsch of Germany for their work on gastrin; E. Jorpes and V. Mutt of Sweden and N. Yahaihara of Japan for their work on secretin and other GI hormones including, CCK, vasoactive intestinal peptide (VIP), gastric inhibitory peptide (GIP), motilin, gastrin-releasing peptide (GRP) and others peptides. CCK and pancreaozymin were found by E. Jorpes and V. Mutt to represent structurally a common messenger for pancreatico-biliary secretion. This rapid development of GI endocrinology in the 1960s and 1970s could be attributed to the application of peptide biochemistry in characterizing various peptide hormones. The technique of radioimmunoassay by S.A. Berson and R.S. Yalow in 1959 measured minute amounts of hormones in the circulation and tissue, and the technique of immunocytochemistry detected the cellular origin of these hormones. Further progress in molecular biology led to sequencing GI hormones and their prohormones, and opened a new area of investigation for the physiological role of these hormones in the mechanism of digestive gland secretion, motility of gastrointestinal tract, visceral blood flow, tissue growth and integrity in health, as well as in various digestive diseases. Overall, apparent divergent concepts, the nervous control (Pavlov) and hormonal control (Bayliss and Starling), greatly facilitated the elucidation of the interacting neuro-hormones during the cephalic, gastric, and intestinal phases of gastric and pancreatic secretion in health and digestive diseases. Although Polish contributions in the early phase of GI endocrinology concerned mostly gastric inhibitory hormones such as enterogastrone and urogastrone, major Polish traces can be detected in the elucidation of origin and physiological role and pathological involvement of gastrin, CCK, secretin, motilin, gastric inhibitory peptide and the most recent additions of enterohormones such as epidermal growth factor, somatostatin, leptin or ghrelin. Major achievements have been obtained in gastric and colorectal cancerogenesis involving gastrin and its precursor, progastrin.

3

Helicobacter pylori infection in gastric cancerogenesis

51%

Konturek P. C., Konturek S. J., Brzozowski T.

Journal of Physiology and Pharmacology

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2009

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tom 60

|

nr 3

3-21

Gastric cancer (GS) remains one of the most common cancers worldwide. It is considered as the second most frequent cause of cancer death worldwide, although much geographical variation in incidence exists. Many studies before linked Helicobacter pylori (Hp) which is now considered as an important pathogen, to the risk of developing noncardia GS. This overview attempts to summarize the recent basic and clinical evidence on the link between H. pylori and gastric cancer, after the award of the Nobel Prize for Physiology or Medicine to Drs. J.R. Warren and B.J. Marshall for the first culture and isolation of Hp and the investigation of their relevance to peptic ulcer disease. It become evident that Hp eradication by antibiotic treatment combined with proton pump inhibitor (PPI) serves as the primary chemoprevention strategy to reduce gastric cancer incidence. Moreover, the eradication therapy reduces gastric cancer incidence in patients without any precancerous lesions at the baseline and is most effective before the development of atrophic gastritis. Due to understanding the molecular nature of GC which has been nowadays under intense investigation, our review attempts to highlight recent progress in the field of research on Hp-induced GS. We discuss the geographical diversity in Hp infection and cancer incidence and the mechanistic role of gastrin, cyclooxygenase-2 (COX-2), growth factor, nitric oxide (NO)/NO synthase and E-cadherin/beta-cathenin systems, apoptosis and angiogenesis in Hp-induced gastric carcinogenesis. In addition host-related genetic susceptibility and the role of overexpression of a proinflammatory cytokines and their polymorphism is discussed in the relation to the cascade of events such as gastric atrophy, intestinal metaplasia and dysplasia that finally lead to adenocarcinoma.

4

COVID-19 - more than respiratory disease: a gastroenterologist’s perspective

51%

Konturek P. C., Harsch I. A., Neurath M. F., Zopf Y.

Journal of Physiology and Pharmacology

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2020

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tom 71

|

nr 2

5

Gastric cancer and Helicobacter pylori infection

51%

Konturek P. C., Konturek S. J., Brzozowski T.

Journal of Physiology and Pharmacology. Supplement

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2006

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tom 57

|

nr 3

51-65

The Nobel prize in Physiology and Medicine in 2005 was presented to Barry Marshall and Robin Warren for their discovery of Helicobacter pylori (Hp), but only the involvement of this germ in gastritis and peptic ulcer has been mentioned in the award sentence, while numerous epidemiological, clinical and experimental studies and reports emphasized the crucial role of Hp in pathogenesis of gastric cancer (GC). This review is based on the old concept proposed by P. Correa much before the discovery of spiral bacteria in the stomach, postulating the cascade of mucosal changes from acute/chronic gastritis into the atrophic gastritis with intestinal metaplasia and finally to dysplasia and GC. It is now widely accepted view that Hp infection is the major initiator of the inflammatory and atrophic changes in gastric mucosa accompanied by an over-expression of certain growth factors such as gastrin as well as of cyclooxygenase-2 (COX-2) and anti-apoptotic proteins including survivin and B-cl2, leading to proliferation of mutated atrophic cells, excessive angiogenesis, inhibition of apoptosis and formation of gastric tumour. All the morphological and biochemical changes associated with the transformation of mucosal cells into the cancer cells can be traced in excellent experimental model of gastric cancerogenesis induced by infection of Hp in Mongolian gerbils. Since the eradication therapy was proved in several prospective clinical trials to greatly reduce the incidence of GC and this was confirmed on the gerbil model of Hp-induced GC, it has been postulated; a) that Hp is the major causal factor in pathogenesis of GC and b) that the only rational approach in attempt to reduce the occurrence of GC is the global eradication of Hp.

6

Hypoglycemic side effects of sulfonylureas and repaglinide in ageing patients - knowledge and self-management

51%

Harsch I. A., Kaestner R. H., Konturek P. C.

Journal of Physiology and Pharmacology

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2018

|

tom 69

|

nr 4

7

Prostaglandins and ulcer healing

51%

Konturek S. J., Konturek P. C., Brzozowski T.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

|

nr 5

5-31

Exogenous prostaglandins (PG) applied in small gastroprotective doses fail to affect healing of gastro-duodenal ulcers but accelerate the healing when used in larger gastric inhibitory doses that appear to enhance COX-2 expression and PGE2 generation in the ulcer area. COX-1 and COX-inhibitors delay ulcer healing, particularly when both COX isoforms are suppressed such e.g. by indomethacin. Dexamethasone, that decreases the expression of COX-2 and mucosal generation of PGE2, delays ulcer healing that can be reversed by the addition of small dose of exogenous PGE2. Proton pump inhibitors (PPI) such as omeprazole and PGE analogs, accelerate ulcer healing mainly due to potent inhibition of gastric acid secretion, but they also augment the COX-2 expression and enzyme activity in the ulcerated mucosa. Endogenous PG generated at ulcer margin appear to be involved in ulcer healing promoted by growth factors and gut hormones such as gastrin or CCK and melatonin acting, at least in part, through increase of induction of COX-2 and local release of PGE2 in the ulcer area . The ulcer healing activity of growth factors (e.g. EGF, TGFalpha, HGF) and certain gut hormones (gastrin, CCK) as well as melatonin, can be attenuated by treatment with COX-1 or COX-2 inhibitors which suppress the release of PGE2 but enhance the expression of COX-2. It is concluded that endogenous PG originating mainly from upregulated COX-2 at the ulcer margin play crucial role in ulcer healing by exogenous PG, PPI, growth factors, gut hormones and melatonin, while COX-1 and COX-2 inhibitors delay ulcer healing by suppressing PG generation, and increasing COX-2 expression in the ulcer area.

8

Gut clock: implication of circadian rhythms in the gastrointestinal tract

51%

Konturek P. C., Brzozowski T., Konturek S. J.

Journal of Physiology and Pharmacology

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2011

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tom 62

|

nr 2

Circadian and seasonal rhythms are a fundamental feature of all living organisms and their organelles. Biological rhythms are responsible for daily food intake; the period of hunger and satiety is controlled by the central pacemaker, which resides in the suprachiasmatic nucleus (SCN) of the hypothalamus, and communicates with tissues via bidirectional neuronal and humoral pathways. The molecular basis for circadian timing in the gastrointestinal tract (GIT) involves interlocking transcriptional/translational feedback loops which culminate in the rhythmic expression and activity of a set of clock genes and related hormones. Interestingly, it has been found that clocks in the GIT are responsible for the periodic activity (PA) of its various segments and transit along the GIT; they are localized in special interstitial cells, with unstable membrane potentials located between the longitudinal and circular muscle layers. The rhythm of slow waves is controlled in various segments of the GIT: in the stomach (about 3 cycles per min), in the duodenum (12 cycle per min), in the jejunum and ileum (from 7 to 10 cycles per min), and in the colon (12 cycles per min). The migrating motor complex (MMC) starts in the stomach and moves along the gut causing peristaltic contractions when the electrical activity spikes are superimposed on the slow waves. GIT hormones, such as motilin and ghrelin, are involved in the generation of MMCs, while others (gastrin, ghrelin, cholecystokinin, serotonin) are involved in the generation of spikes upon the slow waves, resulting in peristaltic or segmental contractions in the small (duodenum, jejunum ileum) and large bowel (colon). Additionally, melatonin, produced by neuro-endocrine cells of the GIT mucosa, plays an important role in the internal biological clock, related to food intake (hunger and satiety) and the myoelectric rhythm (produced primarily by the pineal gland during the dark period of the light-dark cycle). This appears to be an endocrine encoding of the environmental light-dark cycle, conveying photic information which is used by organisms for both circadian and seasonal organization. Motor and secretory activity, as well as the rhythm of cell proliferation in the GIT and liver, are subject to many circadian rhythms, mediated by autonomic cells and some enterohormones (gastrin, ghrelin and somatostatin). Disruption of circadian physiology, due to sleep disturbance or shift work, may result in various gastrointestinal diseases, such as irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD) or peptic ulcer disease. In addition, circadian disruption accelerates aging, and promotes tumorigenesis in the liver and GIT. Identification of the molecular basis and role of melatonin in the regulation of circadian rhythm allows researchers and clinicians to approach gastrointestinal diseases from a chronobiological perspective. Clinical studies have demonstrated that the administration of melatonin improves symptoms in patients with IBS and GERD. Moreover, our own studies indicate that melatonin significantly protects gastrointestinal mucosa, and has strong protective effects on the liver in patients with non-alcoholic steatohepatitis (NASH). Recently, it has been postulated that disruption of circadian regulation may lead to obesity by shifting food intake schedules. Future research should focus on the role of clock genes in the pathophysiology of the GIT and liver.

9

Inhibition of Barrett's adenocarcinoma cell growth by simvastatin: involvement of COX-2 and apoptosis-related proteins

51%

Konturek P. C., Burnat G., Hahn E. G.

Journal of Physiology and Pharmacology. Supplement

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2007

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tom 58

|

nr 3

141-148

10

Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options

51%

Konturek P. C., Brzozowski T., Konturek S. J.

Journal of Physiology and Pharmacology

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2011

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tom 62

|

nr 6

11

Bile acids are multifunctional modulators of the Barrett’s carcinogenesis

51%

Burnat G., Majka J., Konturek P. C.

Journal of Physiology and Pharmacology

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2010

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tom 61

|

nr 2

Bile salts play an important pathogenic role in the development of Barrett adenocarcinoma (BA). However, the precise role of different bile salts in this process is still unknown. The aim of the present study was to compare the effects of two different bile salts, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) on the expression of COX-2, CDX-2 and DNA repair enzymes (MUTYH, OGG-1) in the Barrett epithelial cancer cells (OE-19). OE-19 cells were incubated with DCA or UDCA (100 µM or 300 µM at pH=7.0) over 24 h. To investigate the involvement of NFB, in separate experiments the cells were incubated with DCA in the presence of proteosome inhibitor (MG-132). Cells cycle and apoptosis were analyzed by FACS analysis. After incubation of OE-19 cells with bile salts, the expression of mRNA of COX-2, DNA repair enzymes (MUTYH, OGG-1) and caudal-related homebox transcription factor CDX-2 were measured by quantitative RT-PCR. OE-19 cell were also transfected with siRNA-RelA (p65) to asses effect of NFB inactivation on COX-2 and CDX2 expression. DCA caused a stronger reduction in cell survival of OE-19 cells than UDCA. In addition, DCA stimulated directly the translocation of NFB p65 (active form) in the nuclei of OE-19 cells. DCA caused stronger than UDCA stimulation of the COX-2 mRNA expression in these cells and this effect was significantly attenuated by the addition of inhibitor of NFB activity (proteosome inhibitor MG-132). siRNA-RelA reduced expression not only of NFB but also expression of COX-2 as well as CDX-2 mRNA. DCA caused stronger downregulation of mRNA for DNA repair enzymes MUTYH and OGG-1 than UDCA. In contrast, UDCA induced stronger CDX-2 mRNA expression than DCA in OE-19 cells. We conclude that bile salts are involved in the carcinogenesis of Barrett adenocarcinoma via inhibition of DNA repair enzymes and induction of COX-2 and this last effect is, at least partly, mediated by NFB. DCA shows carcinogenic potential due to high upregulation of COX-2, CDX-2 and downregulation of DNA repair enzymes.

12

Involvement of Helicobacter pylori infection in neuro-hormonal control of food intake

51%

Konturek P. C., Czesnikiewicz-Guzik M., Bielanski W., Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

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2006

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tom 57

|

nr 5

67-81

Ghrelin and leptin are endogenous peptides that have been implicated in the control of food intake, energy homeostasis and body weight gain. Although the stomach is the major source of circulating ghrelin and partly contributes also to plasma leptin, controversy exists over the influence of gastric Helicobacter pylori (Hp) infection on the ghrelin and leptin release. To resolve this controversy, plasma immunoreactive ghrelin and leptin levels were determined in Hp-positive and Hp negative children (N=60) and in adults (N=120) and daily concentrations of these hormones were measured at 2 h intervals before and after meals. Serum levels of ghrelin and leptin as well as gastrin were measured by RIA. Hp status was assessed using 13C-urea breath test (UBT) and serology. Children with negative UBT showed significantly higher basal serum levels of ghrelin and lower concentrations of leptin than those with positive UBT. Adults without Hp infection also showed significantly higher fasting serum levels of ghrelin and lower levels of leptin than those in Hp infected subjects. In adults, especially without Hp infection, plasma levels of ghrelin showed a marked rise before the meal and sudden decrease following the food intake, while plasma leptin did not showed significant meal-related alterations, but in general its level was significantly higher in Hp positive than Hp negative subjects. Serum gastrin concentrations were significantly elevated in both Hp positive children and adults and these levels were significantly lower in Hp negative subjects. We conclude that Hp infection in children and adults causes a marked reduction in plasma levels of ghrelin, while increasing plasma levels of leptin and gastrin. These alterations in plasma levels of gastric originated appetite-controlling hormones in Hp infected children and adults may contribute to the alterations of the appetite and dyspeptic symptoms observed in these subjects.

13

Melatonin in gastroprotection against stress-induced acute gastric lesions and in healing of chronic gastric ulcers

51%

Konturek S. J., Konturek P. C., Brzozowski T.

Journal of Physiology and Pharmacology. Supplement

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2006

|

tom 57

|

nr 5

51-66

The degree of gastric damage following to exposition of the mucosa to noxious agents depends upon a balance between the factors promoting this damage and those activating the natural defense mechanisms. Recent findings, presented in this review, provide evidence that melatonin prevents the formation of acute gastric lesions induced by stress and accelerates healing of chronic gastric ulcers due to increase in the activity of nitric oxide (NO) synthase (NOS)-NO and cyclooxygenase (COX)-prostaglandin E2 (PGE2) systems resulting in the increase of mucosal blood flow and mucosal integrity. Melatonin is produced and released into the circulation by the pineal gland and, in many times larger amounts, by the gastrointestinal tract. Due to its anti-inflammatory and anti-oxidant properties, melatonin may be one of the most efficient protective factors preventing the development of acute gastric damage and accelerating healing of chronic gastric ulcers probably due to reduction in proinflammatory cytokine production, scavenging of the radical oxygen species and activation of COX-PG and NOS-NO systems as well as stimulating the afferent sensory nerves in the brain-gut axis.

14

Role of melatonin in upper gastrointestinal tract

51%

Konturek S. J., Konturek P. C., Brzozowski T., Bubenik G. A.

Journal of Physiology and Pharmacology. Supplement

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2007

|

tom 58

|

nr 6

15

Ascorbic acid attenuates aspirin-induced gastric damage: role of inducible nitric oxide synthase

51%

Konturek P. C., Kania J., Hahn E. G., Konturek J. W.

Journal of Physiology and Pharmacology. Supplement

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2006

|

tom 57

|

nr 5

125-136

Aspirin (ASA) represents an important risk factor for gastric mucosal injury. Recently, vitamin C releasing aspirin (ASA-VitC) has been shown to reduce gastric toxicity of ASA in animal model of gastric injury. The aim of the present study was to compare the effect of ASA and ASA-VitC on the gastric mucosal damage before and after Helicobacter pylori (Hp) eradication in 10 young healthy Hp-positive volunteers. All subjects underwent endoscopy at day 0 (before ASA or ASA-VitC treatment) and at day 3 following treatment (1.6 g ASA/day or 1.6 g ASA + 0.96 g Vit C/day). In addition, in vitro experiments were performed in which gastric mucosal cell line (MKN-45 cells) was incubated with ASA or ASA-VitC alone or in combination with H.pylori. Expression of constitutive and inducible NO synthase (cNOS, iNOS) was analyzed by Western blot. Moreover, COX-2 expression was analyzed in gastric biopsies at mRNA and protein level by RT-PCR and Western blot, repectively. In humans, treatment with ASA-VitC induced significantly less gastric mucosal lesions than plain ASA. Furthermore, in comparision to plain ASA, ASA-VitC caused stronger inhibition of cNOS and increase in iNOS expression in the gastric mucosa. in vitro studies demonstrated a significant increase in iNOS expression in MKN-45 cells incubated with Hp. This effect was aggravated by the addition of ASA, but not ASA-VitC, to MKN-45 cells incubated with H.pylori. Both ASA and ASA-VitC stimulated the COX-2 expression in the gastric mucosa. We conclude that ASA-VitC in comparison with ASA induces less gastric mucosal damage and this protective effect may be due to its inhibitory effect on iNOS expression.

16

NO-releasing aspirin exerts stronger growth inhibitory effect on Barrett's adenocarcinoma cells than traditional aspirin

51%

Konturek P. C., Kania J., Burnat G., Hahn E. G.

Journal of Physiology and Pharmacology. Supplement

|

2006

|

tom 57

|

nr 12

15-24

Expression of cyclooxygenase-2 (COX-2) is involved in the chronic inflammation-related development of Barrett’s adenocarcinoma and the use of selective COX-2 inhibitors (coxibs) might provide new chemoprevention strategy for Barrett’s adenocarcinoma (BA). Despite an excellent gastrointestinal (GI) safety profile of coxibs, their use is limited because of the possible cardiovascular complications. The coupling of NSAIDs with a NO-donating moiety has led to the birth of a new class of anti-inflammatory drugs, called the COX-inhibiting nitric oxide donators (CINODs). The member of this group, NO-aspirin (NO-ASA) retains the anti-inflammatory properties of traditional aspirin (ASA), but the release of NO accounts for anti-thromboembolic effect and better GI safety profile. The role of NO-ASA in the prevention of Barrett’s adenocarcinoma (BA) has not been studied so far. Therefore, the aim of the present study was: 1) to analyse the expression of COX-2 in the biopsies obtained from BE; 2) to compare the effect of NO-ASA with that of ASA on proliferation rate in Barrett’s adenocarcinoma cell line (OE-33 cells); 3) to determine the effect of both compounds on the apoptosis rate using FACS analysis and expression of 32-kDa procaspase-3 and active proapoptotic 20-kDa caspase-3 in OE-33 cell line. The expression of COX-2 was assessed in biopsies obtained from the Barrett’s mucosa and normal squamous epithelial esophageal mucosa from 20 BE patients by RT-PCR and Western blot analysis, respectively. The BA cell line (OE-33) was incubated with NO-ASA or ASA (10-1000µM). The cell proliferation and apoptosis rate was measured by BrdU and FACS-analysis, respectively. The expression of caspase-3 (active and inactive form) was analyzed by Western blot. In Barrett’s mucosa a significant up-regulation of COX-2 was observed. Compared with traditional ASA, NO-ASA caused a significantly stronger induction of apoptosis (dose-dependently). Inhibition of cell proliferation in OE-33 cells observed under NO-ASA treatment was due to the apoptosis induction. The increase in apoptotic rate was accompanied by the upregulation of active 20-kDa caspase-3. At the highest concentration (1000µM), a necrotic death of OE-33 cells was observed under NO-ASA treatment. We conclude that: NO-ASA caused induction of apoptosis in BA cell line and slight growth inhibition. These results indicate that this compound may represent a promising chemopreventive agent for Barrett’s adenocarcinoma.

17

Gastroprotection and control of food intake by leptin. Comparison with cholecystokinin and prostaglandins

51%

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

Journal of Physiology and Pharmacology

|

1999

|

tom 50

|

nr 1

18

The role of reactive oxygen species in action of nitric oxide-donors on stress-induced gastric mucosal lesions

51%

Kwiecien S., Brzozowski T., Konturek P. C., Konturek S. J.

Journal of Physiology and Pharmacology

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2002

|

tom 53

|

nr 4,2

The experimental model of acute gastritis such as water immersion restraint (WRS) stress-induced gastric injury is useful tool in examination of pathomechanism of acute gastritis. Nitric oxide (NO) plays an important role in the maintenance of gastric barrier, however, the interaction between reactive oxygen species (ROS) and NO on gastric mucosal integrity has been little studied. The purpose of our present study was to explain the participation of ROS in healing of WRS-induced gastric lesions accelerated by NO. Experiments were carrying out on 120 male Wistar rats. To assess gastric blood flow (GBF) laser Doppler flowmeter was used and the number of gastric lesions was counted in each stomach. The colorimetric assays were used to determine gastric tissue level of malondialdehyde (MDA) and 4- hydroxynonenal (4-HNE), the products of lipid peroxidation by ROS, as well as superoxide dismutase (SOD) activity, the enzyme scavanger of ROS. We demonstrated that 3.5 h of WRS resulted in appearance of acute gastric lesions accompanied by a significant decrease of GBF. Biological effects of ROS were estimated by measuring tissue levels of MDA and 4-HNE, as well as the SOD activity. It was demonstrated that 3.5 h of WRS led to significant increase of mucosal levels of MDA and 4-HNE, and it was accompanied by a decrease of SOD activity. Pretreatment with NO-donors (SIN-1, SNAP, nitroglycerin, NO-ASA) resulted in reduction in gastric lesion number, increment of GBF, decrease of MDA and 4-HNE tissue level and increase of SOD activity. Suppression of ROS plays an important role in the action of NO-donors on healing of acute gastric lesions induced by 3.5 h of WRS. NO-donors caused an attenuation of lipid peroxidation as documented by a decrease of MDA and 4-HNE levels and enhancement of antioxidative properties as evidenced by an increase of SOD activity.

19

Gastric secretion and the pathogenesis of peptic ulcer in the Helicobacter pylori infection

51%

Konturek P. C., Konturek J. W., Konturek S. J.

Journal of Physiology and Pharmacology

|

1996

|

tom 47

|

nr 1

20

Role of prostaglandins in gastroprotection and gastric adaptation

45%

Brzozowski T., Konturek P. C., Konturek S. J., Brzozowska I., Pawlik T.

Journal of Physiology and Pharmacology. Supplement

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2005

|

tom 56

|

nr 5

33-55

Since Robert discovery that pretreatment with prostaglandin (PG) applied in non-antisecretory dose can prevent the injury of gastric mucosa induced by necrotizing agents, much attention was paid to the role of these cyclooxygenaxe (COX) products in the mechanism of gastric mucosal integrity and ulcer healing. The ability of exogenous PG to attenuate or even completely prevent mucosal damage caused by corrosive substances such as absolute ethanol, hiperosmolar solutions or concentrated bile has been termed "cytoprotection". Increased generation of endogenous PG in the gastric mucosa exposed to the topical contact with "mild irritant" such as 20% ethanol, 1 mM NaCl or 5 mM taurocholate also prevented gastric injury caused by strong irritants via phenomenon of adaptive cytoprotection. Other mediators such as growth factors, nitric oxide (NO) or calcitonin gene related peptide (CGRP) as well as some gut hormones including gastrin and cholecystokinin (CCK), leptin, ghrelin and gastrin-releasing peptide (GRP) have been also found to protect gastric mucosa against the damage induced by corrosive substances. This protective action of gut hormones has been attributed to the release of PG or activation of sensory nerves because it could be abolished by the pretreatment with indomethacin or large neurotoxic dose of capsaicin and restored by the addition of exogenous PGE2 or CGRP, respectively. Short (5 min) ischemia of the stomach applied before prolonged ischemia-reperfusion (I/R) attenuated markedly the gastric lesions produced by this I/R and also prevented the mucosal damage provoked by necrotizing substances. This protection could be abolished by the pretreatment with non-steroidal anti-inflammatory drugs (NSAID) and was accompanied by an enhamcement of gastric mucosal COX-2 expression and activity. Exposure of gastric mucosa to single insult of acidified aspirin (ASA) causes severe mucosal damage with occurence of multiple haemorrhagic lesions but with repeated application of ASA, the attenuation of mucosal lesions is observed, despite the profound inhibition of PGE2 generation. This phenomenon called "gastric adaptation" does not appear to depend upon endogenous biosynthesis of PG but possibly involves enhanced production of growth factors increasing cell proliferation and mucosal regeneration. Unlike short lived gastroprotection by PG, NO, CGRP, mild irritants or short ischemia, gastric adaptation appears to be long-lasting phenomenon accompanied by increased resistance of the adapted mucosa to subsequent damage induced by corrosive agents.

Ograniczanie wyników

Physiological, immunohistochemical and molecular aspects of gastric adaptation to stress, aspirin and to H.pylori - derived gastrotoxins

The history of gastrointestinal hormones and the Polish contribution to elucidation of their biology and relation to nervous system

Helicobacter pylori infection in gastric cancerogenesis

COVID-19 - more than respiratory disease: a gastroenterologist’s perspective

Gastric cancer and Helicobacter pylori infection

Hypoglycemic side effects of sulfonylureas and repaglinide in ageing patients - knowledge and self-management

Prostaglandins and ulcer healing

Gut clock: implication of circadian rhythms in the gastrointestinal tract

Inhibition of Barrett's adenocarcinoma cell growth by simvastatin: involvement of COX-2 and apoptosis-related proteins

Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options

Bile acids are multifunctional modulators of the Barrett’s carcinogenesis

Involvement of Helicobacter pylori infection in neuro-hormonal control of food intake

Melatonin in gastroprotection against stress-induced acute gastric lesions and in healing of chronic gastric ulcers

Role of melatonin in upper gastrointestinal tract

Ascorbic acid attenuates aspirin-induced gastric damage: role of inducible nitric oxide synthase

NO-releasing aspirin exerts stronger growth inhibitory effect on Barrett's adenocarcinoma cells than traditional aspirin

Gastroprotection and control of food intake by leptin. Comparison with cholecystokinin and prostaglandins

The role of reactive oxygen species in action of nitric oxide-donors on stress-induced gastric mucosal lesions

Gastric secretion and the pathogenesis of peptic ulcer in the Helicobacter pylori infection

Role of prostaglandins in gastroprotection and gastric adaptation