Digestion

Arnold, Rudolf; Göke, Burkhard; Schmidt, Wolfgang E.

doi: 10.1159/000201002pmid: N/A

De Lisle, Robert C.

doi: 10.1159/000201003pmid: 8513984

It has become apparent recently that a variety of small GTPases (small GTP-binding proteins or smgs), related to the oncogene ras, are involved in many cellular functions, especially membrane traffic and cytoskeleton regulation. This review will summarize some of the major themes that are emerging, focusing on the presence and possible functions of these smgs in the gastrointestinal tract. In addition, new cellular locations and functions for heterotri-meric G-proteins, previously believed to be solely associated with plasma membrane receptors, are becoming evident and will be discussed here.

Napoli, Nicola; Fiore, Giorgio; Fera, Giacomo; Modugno, Angela; Giannelli, Gianluigi; Manghisi, Onofrio G.; Schiraldi, Oronzo

doi: 10.1159/000201004pmid: 8513991

Rubinstein, E.; Højgaard, L.

doi: 10.1159/000201005pmid: 8513981

The effect of intravenous omeprazole (40 and 80 mg) on the gastric and duodenal potential difference (PD) and pH was investigated in 9 healthy volunteers. Gastric PD and pH increased significantly (p < 0.05) following omeprazole, and the increases were equal following the two doses. No changes were found in duodenal PD or pH. It has been claimed that gastric PD changes following acid secretion inhibition with cimetidine and glucagon might be due to changes in the parietal cell surface area. Omeprazole causes no changes in the parietal cell structure, and the changes in gastric PD following omeprazole might therefore be ascribed to changes in mucosal electrophysiologic transport or resistance.

Marotta, Francesco; Chui, De Hua; Fesce, Edoardo; Rezakovic, Indira; Zhong, Guo Gan; Ideo, Gaetano

doi: 10.1159/000201006pmid: 8513982

In the present study, the effect of graded intravenous infusions of human epidermal growth factor (hEGF) 0.005, 0.05 and 0.25 μg/ml, with or without 4 mg/kg i.p. indomethacin pretreatment, on rat duodenal bicarbonate secretion was investigated. Perfused duodenal loops were prepared in rats which were given intravenous infusions of hEGF with or without indomethacin. Duodenal pH and pCO₂ were measured at 5-min intervals for 45 min, and bicarbonate secretion was calculated. Compared to control, each dose of hEGF caused a significant dose/response rise of duodenal bicarbonate secretion. Prostaglandin release was abolished by indomethacin pretreatment. Indomethacin-pretreated rats had a significant reduction of bicarbonate secretion which was still higher than in controls. These results provide evidence that duodenal bicarbonate secretion induced by hEGF is only partly accounted for by a prostaglandin-dependent mechanism.

Brzozowski, T.; Drozdowicz, D.; Szlachcic, A.; Pytko-Polonczyk, J.; Majka, J.; Konturek, S.J.

doi: 10.1159/000201007pmid: 8513983

Capsaicin and papaverine are potent vasorelaxants with strong gastroprotective activity against damage induced by absolute ethanol. This protection was originally attributed to the increase in gastric mucosal blood flow (GBF) and the present study was designed to determine the possible role of nitric oxide (NO) and prostaglandins (PG) in the protective and hyperemic effects of capsaicin and papaverine on rat gastric mucosa. We found that the pretreatment with capsaicin (0.1-0.5 mg/kg i.g.) or papaverine (0.1-2 mg/kg i.g.) reduced dose dependently the area of ethanol-induced lesions, the ED₅₀ being 0.3 and 1 mg/kg, respectively. This protection was accompanied by a gradual increase in the GBF. Intravenous injection of N^ω-nitro-L-arginine (L -NNA; 1.2-5 mg/kg), a selective blocker of NO synthase, which by itself caused only a small increase in ethanol lesions, reversed dose dependently the protective and hyperemic effects of capsaicin and papaverine against ethanol-induced damage and attenuated the increase in GBF induced by each of these agents alone. This deleterious effect of L -NNA on the gastric mucosa and the GBF was fully antagonized by L -arginine (200 mg/kg i.v.) but not by D-arginine. L -arginine partly restored the decrease in GBF induced by L -NNA. Pretreatment with indomethacin (5 mg/kg i.p.), which suppressed the generation of PG by 85%, slightly enhanced the mucosal lesions induced by ethanol but failed to affect the fall in GBF induced by this irritant. Gastroprotective and hyperemic effects of capsaicin and papaverine were partly reversed by indomethacin suggesting that endogenous PG are also implicated in these effects. Addition of L -NNA to indomethacin completely eliminated both the protective and hyperemic effects of capsaicin and papaverine. We conclude that both NO and PG contribute to the gastroprotective and hyperemic effects of capsaicin and papaverine on the gastric mucosa.

Desai, M.A.; Vadgama, P.M.

doi: 10.1159/000201008pmid: 8513985

The in vitro effect of ammonium bicarbonate buffer on mucus H⁺ permeability is reported here. The diffusional resistance of mucus and water was demonstrated to be dependent on buffer concentration, and the contrast between the two types of layers was most pronounced for low buffer concentration near neutrality. Moreover, the pK_a values of HCO₃^- and NH₃ had a profound effect on measured D_HCl These in vitro studies suggest that a potentially damaging high local concentration of NH₃ and HCO₃^- within the mucus layer generated by the action of Helicobαcter pylori urease on endogenous intragastric urea could greatly accelerate proton flux to the surface epithelium by operation of a buffer shuttle. This results in enhanced H⁺ permeability, particularly at pK_a values of HCO^-₃ and NH₃, and that in extreme circumstances this may result in gastric ulcer formation.

van Wyk, M.; Sommers, De K.; Moncrieff, J.

doi: 10.1159/000201009pmid: 8513986

This study examines the influence of the serotonergic system on the effect of metoclopramide on gastric emptying. Six subjects received the following pre-treatments before metoclopramide and paracetamol: fluoxetine (5-HT uptake inhibitor); meterogoline (5-HT₁ antagonist); pizotifen (5-HT₂ antagonist) or methysergide (5-HT₁ and 5-HT₂ antagonist). One regimen consisted of metoclopramide (5-HT₃ antagonist and 5-HT₄ agonist) alone. Gastric emptying was measured by the mean cumulative fraction absorbed-time profiles of paracetamol. Methysergide/metoclopramide significantly delayed gastric emptying from 30 min onwards. Metoclopramide with either metergoline or pizotifen did not retard gastric emptying to the same extent, suggesting a greater influence with simultaneous 5-HT₁ and 5HT₂ blockade. Metoclopramide/fluoxetine caused a significant decrease in the fractional absorption of paracetamol at 5 min when compared to the metoclopramide regimen. It was assumed that the influence of metoclopramide was not optimal at this stage, therefore possibly indicating domination of 5-HT₃ over 5-HT₄ effects, resulting in gastric delay. It therefore seems as if all the 5-HT receptors present in the gut have a role to play in the control of gastric emptying.

Tulassay, Zsolt; Tulassay, Tivadar; Gupta, Ramesh; Rascher, Wolfgang

doi: 10.1159/000201010pmid: 8513987

The significance of atrial natriuretic peptide (ANP) was investigated in the maintenance of the fluid volume in hypovolemia associated with dumping syndrome following gastric resection. The study was performed on 10 patients who had undergone a Billroth II procedure. Ten age- and sex-matched patients without previous gastric surgery served as control. Each patient underwent an oral glucose challenge. The patients with gastric resection underwent another glucose challenge with intravenous infusion to maintain the fluid volume. All patients with gastric resection showed subjective symptoms of the early dumping syndrome with significant (p < 0.001) increases (initial and maximum rates; mean ± SD) in heart rate (from 70 ± 3 to 122 ± 4 beats/min) and in hematocrit (from 0.40 ± 0.005 to 0.45 ± 0.003). The plasma ANP level decreased significantly from 27.24 ± 5.01 to 15.94 ± 3.61 fmol/ml (p < 0.01). A significant negative correlation was found between the changes in hematocrit and the changes in plasma ANP level (r = 0.68; p < 0.001). Neither the subjective symptoms characteristic of the early dumping syndrome nor changes in laboratory parameters were noted in the patients during the challenge with infusion. The results show that the hypovolemia in dumping syndrome is associated with a significant decrease in ANP activity. The regulation of ANP release is also affected: apart from the well-known stimulating effect of hypervolemia, there exists an inhibition of secretion in volume-depleted states.

Lam, W.F.; Masclee, A.A.M.; de Boer, S.Y.; Lamers, C.B.H.W.

doi: 10.1159/000201011pmid: 8513988

We have investigated the effect of acute stable hyperglycemia on gastric acid secretion and serum gastrin and pancreatic polypeptide (PP) release. Gastric acid output was measured under basal conditions and in response to modified sham feeding (MSF) in 7 healthy volunteers on two separate occasions: during normoglycemia (serum glucose 5 mmol/l) and during hyperglycemia (serum glucose 15 mmol/l). PP secretion was determined as an indirect measure of vagal-cholinergic tone. Basal acid output during hyperglycemia (4.7 ± 1.0 mmol/h) was not significantly different from euglycemia (5.4 ± 0.6 mmol/h), but MSF-stimulated acid output during hyperglycemia (14.7 ± 3.3 mmol/90 min) was significantly (p < 0.05) reduced compared to euglycemia (24.7 ± 3.2 mmol/90 min). Serum gastrin levels were not affected by MSF. During hyperglycemia, the integrated PP secretion in response to MSF (235 ± 95 pmol/l · 90 min) was significantly (p < 0.05) reduced compared to euglycemia (434 ± 71 pmol/l · 90 min). This study indicates that (1) serum glucose affects cephalic-stimulated gastric acid secretion, and (2) PP secretion after MSF is significantly reduced during hyperglycemia suggesting impaired vagal-cholinergic activity during hyperglycemia.