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Biomedical subjects

G Flemström

Publications and source records attributed to G Flemström.

At least 55 records · Page 3Linked to original sources
PubMed1986

Vagal stimulation of duodenal HCO3(-)-secretion in anaesthetized rats.

The present study was designed to examine the influence of the vagal nerves on mucosa protective duodenal HCO3(-)-secretion in chloralosed rats. The HCO3(-)-secretion was measured by in situ titration in a duodenal segment devoid of Brunner glands. Cervical vagotomy lowered duodenal HCO3(-)-secretion and stimulation of the cut vagal nerves (10 Hz for 15 min) increased this secretion. Both basal and vagally stimulated duodenal HCO3(-)-secretions were more pronounced in rats with ligated adrenal glands. Atropine did not influence basal duodenal HCO3(-)-secretion, whereas indomethacin and hexamethonium lowered basal secretion in vagotomized rats with ligated adrenal glands. Compared with untreated controls, vagally induced secretory responses were unchanged by atropine, 50% smaller in indomethacin treated rats and almost abolished in rats treated with hexamethonium. The study suggests that the vagal nerves exert an excitatory effect on duodenal HCO3(-)-secretion which is mainly mediated via nicotinic, non-muscarinic transmission, in part dependent on prostaglandin synthesis. Furthermore, the results indicate that the adrenal glands exert an inhibitory action on both the basal and vagally induced mucosa protective HCO3(-)-secretion.

Adrenal Glands↗
PubMed1986

Gastroduodenal mucosal secretion of bicarbonate and mucus: physiological control and role in protection.

Bicarbonate secretion by the surface epithelium in the stomach and duodenum maintains a near neutral pH in the mucus gel adherent to the surface in spite of acidities as high as pH 2.0-3.0 in the gastric and pH 1.5-2.0 in the duodenal lumen. This strongly suggests that the alkaline secretion together with the mucus gel provides a first line of protection in the stomach and this may be the main mechanism of defense in the duodenum. The secretion is increased by physiological stimuli such as sham-feeding or the presence of acid in the lumen. Mucosal endogenous production of prostaglandins as well as humoral and neural mechanisms are involved in the control of the secretion.

Animals↗
PubMed1985

Gastroduodenal bicarbonate secretion in mucosal protection. Possible role of vasoactive intestinal peptide and opiates.

HCO3- secretion by surface epithelium in duodenum devoid of Brunner's glands was titrated in situ in anesthetized rats. Intravenous injection of small amounts (20 ng/kg) of the endogenous opioid peptide beta-endorphin significantly increased secretion. Naloxone prevented this effect, suggesting that stimulation is mediated by mu-opiate receptors. Morphine 50 microgram/kg had a similar stimulatory action. Vasoactive intestinal peptide (VIP) 0.5-100 microgram/kg dose-dependently increased secretion and this response was independent of simultaneous cholinergic stimulation. The HCO3- secretion maintained pH in the mucus gel adherent to the luminal surface at neutrality for long periods of time (greater than or equal to 60 min); even when the pH in the terminal bulk solution was as low as 2.0. Mucosal HCO3- secretion is thus very probably important in mucosal protection and VIP and endogenous opioid peptides may have a role in its control.

Animals↗
PubMed1985

Cysteamine and propionitrile inhibit the rise of duodenal mucosal alkaline secretion in response to luminal acid in rats.

Effects of subulcerogenic doses of cysteamine (100 mg/kg s.c.) and propionitrile (5 mg/kg) on alkaline secretion by duodenal surface epithelium and pH at the surface of this mucosa were assessed in duodenum of anesthetized rats. Alkaline secretion was titrated in situ, using segments of duodenum just distal to the Brunner's glands area and devoid of pancreatic HCO3-. Surface pH was measured by advancing pH-sensitive microelectrodes from the luminal solution to the epithelial cell surface. Proximal duodenum from bullfrogs was used to study effects of cysteamine on alkaline secretion in vitro. Cysteamine caused an increase in alkaline secretion in the rat during the first hour after administration, but rates after 5 and 20 h were the same as in controls and cysteamine (1 mg/ml) had no effect on secretion in vitro. Neither in vitro nor in vivo did cysteamine affect the rise in alkaline secretion in response to exogenous prostaglandin E2 (and dibutyryl-cyclic adenosine monophosphate). Luminal acid is a potent stimulant of duodenal mucosal alkaline secretion. By delayed (5 h) actions, both cysteamine and propionitrile inhibited the rise in alkaline secretion in response to a 5-min exposure to luminal acid with pH 2.00 in the rat. Cysteamine also depressed the ability of this mucosa to maintain a high rate of alkaline secretion during sustained exposure at pH 2.00 but had no such effect at pH 5.00. The former resulted in acidification of the pH gradient at the mucosal surface. Cysteamine is thus probably without effect on the HCO3- secretory process itself but impairs the ability of the duodenal mucosa to respond to acid. Inhibition of mechanisms mediating this response may contribute to the duodenal ulcerogenic actions of cysteamine and propionitrile.

2,4-Dinitrophenol↗
PubMed1985

Effects of some opiates and vasoactive intestinal peptide (VIP) on duodenal surface epithelial bicarbonate secretion in the rat.

Bicarbonate secretion by 12 mm segments of duodenum just distal to the Brunner's glands area and devoid of pancreatic bicarbonate was titrated in situ in anaesthetised rats. The secretion increased significantly after intravenous injection of small amounts (20 ng/kg) of the endogenous opioid peptides beta-endorphin and methionine enkephalin and maximal (approximately twofold) stimulation occurred after 200-500 ng/kg. Morphine (50 micrograms/kg) caused a similar stimulation and the mu-opiate antagonist naloxone prevented stimulation by morphine. The synthetic analogue [D-Ala2, D-Leu5]-enkephalin (500 ng/kg) which is an agonist at delta-opiate receptors, did not affect the secretion, further suggesting that stimulation is mediated by mu-receptors. VIP (5-100 micrograms/kg) increased the secretion dose-dependently to levels considerably higher than those observed with opiates, and pretreatment with atropine or indomethacin did not affect the response to VIP. The results suggest a role of endogenous opioid peptides and VIP in the humoral and/or nervous control of duodenal surface epithelial bicarbonate secretion and mucosal protection.

Animals↗
PubMed1984

Some characteristics of duodenal epithelium.

Duodenum is exposed to potential damage from acidopeptic secretions emptied from the stomach. In several mammalian species the duodenal mucosa was shown some 50 years ago to be better able to resist acid gastric juice than mucosa in more distal small intestine. Recent studies have identified HCO3- secretion originating from the surface epithelium, together with the ability of this epithelium to respond to intraluminal acid with a rise in HCO3- secretion, as important components of duodenal mucosal protection. Whether duodenal (Brunner's) glands also secrete some HCO3- is at present unknown. Secretion of HCO3- is stimulated up to 10-fold by the presence of luminal acid and is quantitatively sufficient to maintain neutrality at the mucosal cell surface at the lowest pH values encountered in the duodenum (approximately pH 2.0). Stimulation is mediated by mucosal production of prostaglandins, humoral factors and possibly neural mechanisms. The mucus gel adherent to the mucosa provides a physical basis for the standing pH gradient generated by epithelial HCO3- secretion. In vivo, mucosal blood flow supplies HCO3- to the epithelial cells and is particularly important at high (stimulated) rates of secretion.

Animals↗
PubMed1984

Stimulation of mucosal bicarbonate secretion in rat duodenum in vivo by BW755C.

Bicarbonate secretion from 12 mm segments of duodenum just distal to the Brunner's gland area was titrated (pH 7.60) in situ in anesthetized rats. Intravenous BW755C (10-20 mg/kg) increased both bicarbonate secretion and the transmucosal electrical potential difference and pretreatment with indomethacin (3 mg/kg intravenously) prevented these effects. Indomethacin also inhibited stimulation of HCO3- secretion by luminal acid (10 mM HCl) but had no effect on the rise in secretion in response to exogenous (luminal) prostaglandin E2. The results support previous suggestions of a role for endogenous prostaglandins in mediation of the HCO3- response to acid and are consistent with the recent demonstration that BW755C increased prostaglandin formation in homogenates of rat intestinal mucosa. Stimulation of HCO3- secretion by BW755C was not enhanced but attenuated by preexposure to luminal acid, suggesting that the latter increases secretion by effects other than mucosal mobilization of arachidonate.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1984

Regulation of gastroduodenal HCO-3 transport by luminal acid in the frog in vitro.

Luminal acid (10 mM HCl) is a stimulant of surface epithelial HCO-3 transport in mammalian stomach and duodenum in vivo. To determine whether a humoral mechanism is involved in mediation of this response, amphibian fundic, antral, or proximal duodenal mucosae were mounted in parallel in an in vitro chamber with their nutrient (serosal) surfaces facing a common solution. The mucosal surfaces were bathed by separate solutions and the rate of HCO-3 transport by one mucosa titrated (at pH 7.40) during exposure of the parallel tissue to luminal acid. In studies of fundic HCO-3 transport, H+ secretion was inhibited with the histamine H2-antagonist tiotidine (10(-4) M). Fundic luminal acid stimulated HCO-3 transport by a parallel fundus (27 +/- 6%) or antrum (53 +/- 27%) but had no effect on a parallel duodenum. Antral luminal acid had no effect on a parallel antrum, indicating that the gastric stimulant is of fundic origin. Duodenal luminal acid increased HCO-3 transport by both parallel duodenum (21 +/- 5%) and fundus (109 +/- 32%). Stimulation of HCO-3 transport occurred at higher luminal pH in duodenum (approximately 4.0) than in fundus (approximately 2.0). Thus, exposure to luminal acid releases humoral factor(s) capable of stimulating surface epithelial HCO-3 transport by both stomach and duodenum. The actions of these putative stimulants are in part tissue specific, and they may be important in mediation of mucosal protection against luminal acid.

Animals↗
PubMed1984

Gastric mucosal protective mechanisms: roles of epithelial bicarbonate and mucus secretions.

Secretion of HCO3 (amounting to 2-10% of maximum H+ secretion) in conjunction with the adherent mucus gel layer (functioning as a mixing barrier) protects gastric mucosa from luminal acid by a process of surface neutralization. Gastric HCO3 secretion is augmented by cholinergic agonists, prostaglandins and low luminal pH. Ulcerogens attenuate HCO3 secretion although passive diffusion of alkali consequent upon an increase in mucosal permeability may mask these inhibitory actions. Studies in vitro indicate that HCO3 transport in the stomach is dependent on oxidative metabolism, carbonic anhydrase activity and involves a CL exchange mechanism. Mucus, synthesized and released from epithelial cells, adheres to the mucosal surface as a thin (less than 80 microns in rat) but continuous gel layer. Prostaglandins and carbachol induced release of preformed mucus and thereby increase thickness, whereas acute exposure to ulcerogens has little effect on overall dimensions of the surface mucus layer. Measurements of pH gradients adjacent to gastric mucosa indicate that the disposal of luminal H+ occurs by extracellular neutralization. However, the fall in pH at the apical cell membrane when luminal pH is low (pH 1.5) suggests that while a mucus-bicarbonate barrier comprises the first line of mucosal defence, other factors are involved in the overall process of mucosal protection in the stomach.

16,16-Dimethylprostaglandin E2↗
PubMed1984

Gastroduodenal defence mechanisms.

In the healthy stomach and duodenum aggressive factors such as luminal acid and pepsin are balanced by defence and repair processes. In recent years components of the mucosal defences which have been identified include the layer of mucus gel adherent to the surface of these mucosae, surface epithelial alkali secretion, mucosal blood flow and the supply of bicarbonate to the surface epithelium as well as the processes involved in rapid mucosal repair. Secretion of alkali maintains the pH within the mucus gel on the epithelial cell surface at neutrality, in spite of luminal pHs as low as 1.5 to 2.0. Alkali secretion is stimulated up to ten-fold by luminal acid. This response is mediated by endogenous production of prostaglandins, humoral factors and, possibly, by nervous mechanisms. Impairment of the response results in mucosal ulceration. The mucus layer (approximately 200 micron deep in man) provides an unstirred zone at the mucosal surface in which diffusing is delayed, allowing time for secreted HCO-3 to neutralize acid diffusing toward the mucosa. In addition mucus is impermeable to pepsin. During secretion of H+ ions, HCO-3 is produced, and secreted by the surface epithelium. Stimulation of acid secretion increases the ability of gastric mucosa to resist acid and pepsin, presumably by providing more HCO-3. Parenteral HCO-3 (but not other buffer species) provides similar protection to both the gastric and duodenal mucosae. The remarkably rapid reconstitution of the surface epithelium, within 30 minutes after acute superficial damage, is clearly an important 'defence' mechanism. Studies of the control of these defence and repair mechanisms should provide a greater understanding of common gastroduodenal diseases.

Animals↗
PubMed1984

Stimulation by BW755C and inhibition by cysteamine of duodenal epithelial alkaline secretion suggest a role of endogenous prostaglandin in mucosal protection.

Alkaline secretion by 12 mm segments of duodenum just distal to the Brunner's glands area was titrated in situ in anesthetized rats. Intravenous injection of the lipoxygenase inhibitor BW755C (10-20 mg/kg) increased the surface epithelial HCO3- secretion and pretreatment with indomethacin prevented this effect. This supports the view that endogenous production of prostaglandins is important in control of duodenal epithelial HCO3- secretion and ulceroprotection . Pretreatment with cysteamine (100 mg/kg) inhibited the ability of the duodenal surface epithelium to respond to luminal acid with a compensatory rise in alkaline secretion. Measurement of pH at the mucosal surface with microelectrodes revealed that acidification of this surface occurred simultaneously with the decline in alkaline secretion.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1984

Current concepts of gastroduodenal mucosal protection.

Mucosal protection against luminal acid and pepsin and recovery from acute damage in the upper gastrointestinal tract depends upon a number of interrelated mechanisms. The thin adherent mucus gel layer protects against shear and luminal pepsin and provides a mixing barrier for surface neutralization of H+ by HCO3- secreted from the underlying epithelia. Gastric HCO3- transport amounts to 2-10% of maximum H+ rate and involves a Cl- exchange mechanism. The rate of duodenal HCO3- transport is some 5-fold greater and both Cl- exchange and transcellular secretion of HCO3- occur. Blood flow ensures adequate oxygenation, provides a pool of HCO3- and maintains mucosal acid-base balance. Gastroduodenal mucosa has a high proliferative rate and in the stomach, the process of continual cell replacement is augmented by restitution of epithelial integrity following acute damage.

Animals↗
PubMed1984

HCO3- secretion and surface pH gradient in rat duodenum exposed to luminal acid.

A pH gradient is maintained at the surface of rat duodenum exposed to luminal acid. The alkalinity and thickness of this gradient are dependent on the rate of surface epithelial HCO3- secretion (transport into the lumen). Acidification of the luminal solution stimulates HCO3- secretion and enhances the alkalinity at the mucosal surface by a mechanism dependent on endogenous prostaglandin synthesis. This stimulated HCO3- secretion is quantitatively sufficient to maintain neutrality at the epithelial surface of the mucosa even in the presence of as high luminal acidity as pH 2.0, which is the maximal 'physiologic' acidity within human duodenal bulb. Exogenous prostaglandin E2 increases HCO3- secretion as well as the dimensions of the pH gradient, which may, in part, account for its cytoprotective actions in gastroduodenal mucosa. The findings suggest that epithelial HCO3- secretion in the duodenal mucosa has a protective function by forming an unstirred alkaline layer at the mucosal surface which impedes the diffusion of luminal acid into the mucosa.

Acetazolamide↗