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G Flemström

Publications and source records attributed to G Flemström.

At least 73 records · Page 4Linked to original sources
PubMed1983

Demonstration of a pH gradient at the luminal surface of rat duodenum in vivo and its dependence on mucosal alkaline secretion.

The relationship between surface epithelial alkaline secretion and pH at the mucosal cell surface was studied in the duodenum of anesthetized rats. Alkaline secretion was measured by direct titration in situ using perfused segments of duodenum just distal to the Brunner gland area and devoid of pancreatic and biliary HCO3-. Mucosal surface pH was measured by advancing a pH-sensitive antimony microelectrode from the luminal solution to the mucosal cell surface during continuous recording of pH. Acidification of the luminal solution markedly stimulated epithelial alkaline secretion: a change of luminal pH from 7.60 to 5.00 by approximately 100%, and from pH 7.60 to 2.00 by approximately 600%. Maximal pH in the immediate vicinity of the (luminal) cell surface remained at or slightly above neutrality during exposure to both luminal acidities. Prostaglandins (E2, 16,16-dimethyl E2, and F2 alpha, 3-140 microM luminally) increased the rate of alkaline secretion, surface alkalinity, and thickness of the pH gradient. Acetazolamide (40-80 mg/kg, i.v.) was a much more potent inhibitor of prostaglandin or acid-stimulated secretion than of basal alkaline secretion and decreased surface pH in acid-exposed duodenum. Aspirin (30 mg/kg, i.v.) had no effect on basal alkaline secretion (titrated at luminal pH 7.60) but significantly inhibited secretion at luminal pH 2.00, resulting in a decrease of surface pH. These data suggest that endogenous prostaglandins may be involved in mediating the alkaline response to luminal acid. Furthermore, because it is quantitatively sufficient to maintain neutral pH at the mucosal cell surface at luminal acidities normally encountered within the duodenal bulb, epithelial alkaline secretion presumably has an important role in duodenal protection against acid.

Acetazolamide↗
PubMed1982

Gastric and duodenal HCO3- transport in vitro: effects of hormones and local transmitters.

Luminal application of acid was recently shown to stimulate surface epithelial HCO3(-) transport in stomach and duodenum. Effects of some potential transmitters of this response were therefore studied in amphibian gastric fundic and proximal duodenal mucosa in vitro. Duodenal HCO3- transport, which could be titrated directly, was stimulated by dibutyryl cAMP (DBcAMP, 10(-6) M), the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-6) M), noradrenaline (10(-6) M), pancreatic glucagon (10(-8) M), and gastric inhibitory peptide (GIP, 10(-10) M). Stimulation by glucagon, but not by prostaglandin E2 (PGE2, 10(-6) M), required Cl- in the luminal solution and was prevented by furosemide (10(-3) M). This suggests that glucagon may affect HCO3(-)-Cl- exchange at the luminal membrane while transport stimulated by prostaglandins may be electrogenic. Stimulatory effects of glucagon and PGE2 were also additive. Gastric HCO3- transport, studied in tissues after inhibition of H+ secretion by histamine H2-antagonists, clearly differed from duodenum in that noradrenaline and GIP were inhibitory and DBcAMP was without effect. Stimulation of gastric HCO3- transport was observed with glucagon (10(-8) M), natural cholecystokinin (CCK, 10(-8) M), and CCK octapeptide (10(-7) M), CCK preparations had no effect in the duodenum. Although tested over a wide range of concentrations, no effect on either duodenal or gastric HCO3- transport was observed with histamine, pentagastrin, tetragastrin, urogastrone, ACTH, bombesin, motilin, secretin, serotonin, somatostatin, substance P, or vasoactive intestinal peptide.

Animals↗
PubMed1982

Surface epithelial HCO3(-) transport by mammalian duodenum in vivo.

Duodenal surface epithelial transport of HCO3(-) was measured by direct titration in anesthetized animals. Alkalinization of the lumen occurred in all species, although basal rates varied considerably: rats (approximately 10), cats (approximately 15), pigs (approximately 25), dogs (approximately 25), guinea pigs (approximately 40), and rabbits (approximately 170 mueq.cm-1.h-1). In cats duodenum transported HCO3(-) at a greater basal rate than jejunum (approximately 5 mueq.cm-2.h-1) and developed a higher transmucosal electrical potential difference (PD, lumen negative). Luminal application of 10 mM HCl for 5 min produced a sustained increase in the rate of duodenal HCO3(-) transport that was accompanied by a rise in appearance of E-like prostaglandin immunoreactivity in the lumen and a decrease in DNA release. In cats pretreated with indomethacin (10 mg/kg iv), acid caused only a transient increase in HCO3(-) transport. Exogenous prostaglandin E2 (1-12 microM, luminal) increased basal HCO3(-) transport in cats, rats, and dogs but had no effect on this transport in guinea pigs and rabbits. However, prostaglandin E2 increased HCO3(-) transport and PD in guinea pigs pretreated with inhibitors of tissue cyclooxygenase activity (indomethacin or aspirin) or gastric H+ secretion (cimetidine). Thus the continuous exposure of the duodenum of herbivores to HCl discharged from the stomach may itself stimulate HCO3(-) transport via an increase in endogenous prostaglandin levels and render exogenous prostaglandins ineffective. Secretin (1-15 CU/kg iv) was without effect in both cats and guinea pigs. In guinea pigs, intravenous glucagon (120-360 micrograms.kg-1.h-1) or gastric inhibitory peptide (5 micrograms/kg) both increased HCO3(-) transport but not PD. Hence, prostaglandin-stimulated and hormone-stimulated mechanisms of HCO3(-) transport probably occur in mammalian duodenum as found previously in the isolated amphibian duodenum. The results suggest that epithelial HCO3(-) transport is a major mechanism of acid disposal, and thus mucosal protection, in mammalian duodenum under the control of hormones and endogenous prostaglandins.

Animals↗
PubMed1981

Stimulation of duodenal epithelial HCO3- transport in the guinea pig and cat by luminal prostaglandin E2.

Segments of guinea pig or cat duodenum distal to the Brunner gland containing area and devoid of bile or pancreatic secretions were cannulated in situ. The unbuffered luminal solution was gassed with 100% O2 or N2 and HCO3- transport titrated at pH 7.40 or 8.00 with solutions containing HCl. Cat duodenum transported HCO3- at a greater rate (approximately 17 mueq, cm-1, h-1) than did jejunum in the same animals (approximately 5 mueq, cm-1, h-1) and also developed a greater transmucosal electrical potential difference. Luminal application of PGE2 (1-12 micrometers) in cat duodenum increased HCO3- transport and the potential difference. HCO3- transport by guinea pig duodenum (approximately 27 mueq cm-1, h-1) was increased by luminal PGE2 only in animals where transport had been inhibited by pretreatment with aspirin (30 mg/kg intravenously). Exposure of the cat duodenal lumen to HCl (1-25 mM, 5 min) stimulated HCO3- transport and continuous exposure of duodenum in the guinea pig to acid discharged from the stomach may increase endogenous prostaglandin concentrations, resulting in an apparent lack of effect of exogenous prostaglandins. The present results and previous similar findings in amphibians in vitro suggest that surface epithelial transport of HCO3- protects duodenal mucosa against acid.

Animals↗
PubMed1981

Effect of parathyroid hormone on bicarbonate secretion in the guinea-pig stomach and the amphibian isolated gastric mucosa.

1. The effect of parathyroid hormone on gastric bicarbonate secretion was determined in the anaesthetized guinea pig. Subcutaneous injections of bovine parathyroid hormone (75 U.S.P units day-1 kg-1) for 7 days caused a significant increase in HCO3- output. There was also a rise in K+ output and a slight elevation of H+ secretion. A similar increase in HCO3- output occurred after acute intravenous injection of the hormones (75 U.S.P. units/kg). 2. Both chronic and acute administration of parathyroid hormone caused a significant increase in serum calcium concentration and it is likely that the changes in gastric ion outputs reflect raised calcium levels. Given alone intravenous calcium (1.5 mg/kg body wt.) stimulated gastric secretion of both HCO3- and H+. 3. To determine whether parathyroid hormone had a direct action on gastric ion transport experiments were performed in the amphibian isolate mucosa. Antrum transports HCO3- spontaneously while HCO3- transport in fundus was studied after inhibition of the greater H+ secretion by the histamine H2-receptor antagonist metiamide. Parathyroid hormone at a concentration of 0.2 United States Pharmacopea (U.S.P.) unit/ml in the nutrient-side bathing solution inhibited both antral and fundic HCO3- transport. A higher concentration (2.0 units/ml) had no effect on fundic H+ secretion. 4. The inhibitory effect in vitro was greater in the antrum and parathyroid hormone may almost abolish the active component of HCO3- transport in this tissue. It is likely that any similar inhibition of gastric HCO3- secretion by parathyroid hormone in vivo is masked by the stimulatory effects of released calcium.

Animals↗
PubMed1981

Effect of carbenoxolone on alkaline secretion by isolated amphibian gastric and duodenal mucosa.

The influence of carbenoxolone sodium on HCO-3 transport has been examined in spontaneously alkalinizing amphibian antral (Necturus and Rana catesbeiana) and proximal duodenal (Rana catesbeiana) mucosa and in cimetidine-treated fundic mucosa (Rana temporaria) in vivo. Low concentrations of carbenoxolone (10(-6)-10(-4) mol/l, serosal side and 10(-5) mol/l, luminal side) did not affect the secretory rate or electrical properties of these tissues. In the stomach a higher concentration of carbenoxolone (10(-3) mol/l, serosal side) caused an immediate fall in transmucosal potential difference (PD) and electrical resistance. There was an initial decrease in the rate of HCO-3 transport followed by an increase in titratable alkalinization due to passive permeation of base from the serosal bathing solution. The non-steroidal anti-inflammatory agent ibuprofen (3 x 10(-3) mol/l, serosal side) inhibited alkaline secretion while the bile salt sodium taurocholate (10(-4) mol/l, luminal side) converted net alkaline secretion to a titratable acidity in cimetidine-treated fundus. Pretreatment of the mucosa with carbenoxolone (10(-4) mol/l) did not influence the response to taurocholate but when added with ibuprofen it potentiated the inhibitory effect of this drug on fundic alkaline secretion. In contrast, prostaglandin E2 (10(-6) mol/l) markedly reduced the inhibition of fundic alkaline secretion caused by ibuprofen. The anti-ulcer properties of carbenoxolone do not appear to be related to effects on gastroduodenal HCO-3 transport.

Animals↗
PubMed1980

Stimulation of gastric acid and bicarbonate secretions by calcium in guinea pig stomach and amphibian isolated mucosa.

Administration of Ca++ (1.5 mg/kg i.v.) increased the output of both H+ and HCO-3 from the stomach of the anesthetized guinea pig as determined by measurement of gastric intraluminal pH and pCO2. The rise in HC-3 secretion was slightly greater than that in H+, resulting in a decrease in net acidity. Fundic mucosa isolated from frogs was used to study the mechanisms of the stimulatory actions. An increase in Ca++ concentration in the nutrient (serosal) bathing solution from 1.8 to 7.2 mM stimulated H+ transport in this preparation. The effect of raising Ca++ concentration was inhibited by the histamine H2 receptor antagonist Metiamide and by increasing nutrient Mg++. Stimulation of H+ transport, sensitive to Metiamide, was also observed with the calcium ionophore A23187 (4 micrograms/ml, nutrient side). The results indicate that at the mucosal level, Ca++ stimulates H+ transport by release of histamine from mucosal stores with properties similar to those of mast cells. Transport of HCO-3 in isolated mucosae was studied after inhibition of H+ transport my metiamide. An increase in nutrient Ca++ concentration stimulated the HCO-3 transport but the calcium ionophore had no effect. This action of Ca++ was abolished by atropine (10(-6) M) and by raising nutrient Mg++, suggesting that it reflects release of acetylcholine from intramucosal nervous tissue. Thus Ca++ stimulated gastric transport of both H+ and HCO-3 in vivo and in vitro but evidence for a direct action on the transporting (parietal and epithelial) cells was not obtained.

Animals↗
PubMed1980

Stimulation of HCO3- transport in isolated proximal bullfrog duodenum by prostaglandins.

An in vitro preparation of proximal duodenum from the bullfrog transported alkali into the luminal solution (approximately 1 mueq x h-1 x cm-2) and generated a transepithelial electrical potential difference (5-10 mV, lumen negative). Transport was inhibited by 2,4-dinitrophenol (10(-5) M), CN- (5 X 10(-3) M), indomethacin (5 X 10(-5) M), and acetazolamide (5 X 10(-3) M) indicating that metabolism is required. Both alkali transport and the electrical potential difference showed a dose-dependent increase on administration of the prostaglandins E2, 16,16-dimethyl E2, and F2 alpha. The minimal concentration stimulating transport was lower with the E-type prostaglandins (10(-8) M than with F2 alpha (10(-6) M), and the former also produced greater maximal responses. In addition to metabolic-dependent transport of alkali, there was passive transmucosal migration of HCO3-, amounting to approximately 40% of basal (unstimulated) transport and sensitive to variation of the transmucosal hydrostatic pressure. Morphological examination showed that the preparation is devoid of Brunner glands. Stimulation of duodenal epithelial HCO3- transport by prostaglandins may contribute to their previously demonstrated ability to prevent duodenal ulceration.

Acetazolamide↗
PubMed1980

Cl- dependence of HCO3- transport in frog gastric mucosa.

Frog (Rana temporaria) fundic mucosae in vitro were pretreated with the histamine H2 receptor antagonist Metiamide (10(-3)M, nutrient side) until net H+ secretion had ceased and a steady rate of HCO3- transport (luminal alkalinization) was titrated. Removal of Cl- with SO4(2) or isethionate replacement from solutions bathing both sides of the mucosa abolished luminal alkalinization. Readdition of Cl- to the luminal side only reestablished full rates of HCO3- transport. Nutrient (serosal) side Cl- had no effect in this aspect. The results support the previous suggestion that the gastric HCO3- transport process is located at the luminal membrane of the surface epithelial cells and indicate that it occurs by (electroneutral) HCO3-/Cl- exchange.

Animals↗
PubMed1979

Kinetics of acetylsalicylate and D-lactate transport across isolated frog gastric mucosa.

Luminal to submucosal migration of 14C-acetylsalicylate and D-lactate and some electrical properties were studied in isolated frog gastric mucosae. With both compounds, the unionized acids permeated much more rapidly than the ionized conjugate bases. The permeability coefficient for unionized acetylsalicylic acid increased from 0.27 to 0.43 mumoles, h-1, cm-2, mM-1 when its luminal concentration was increased above 3 mM. Simultaneously there was an increase in mucosal ion conductance. Acetylsalicylic acid has been shown previously to increase gastric mucosal permeation of ions and uncharged larger molecules. The present results indicate that above a threshold concentration the unionized form also enhances absorption of this drug per se. Unionized D-lactic acid had no effect of mucosal ion conductance and the permeability coefficient (0.07 mumoles, h-1, cm-2, mM-1) was independent of its luminal concentration.

Animals↗
PubMed1979

Effects of antiinflammatory agents and prostaglandins on acid and bicarbonate secretions in the amphibian-isolated gastric mucosa.

Effects of antiinflammatory agents and prostaglandins on H+ and HCO-3 secretions and electrical properties were investigated in the amphibian-isolated gastric mucosa. Gastric HCO-3 transport was studied in Rana temporaria fundus, in which H+ secretion had been inhibited with the histamine H2-receptor antagonists metiamide or cimetidine (10(-3) M), and in Necturus antrum, which secreted HCO-3 spontaneously. Hydrocortisone (100-500 microgram/ml) had no effect on H+ or HCO-3 secretion in the fundus. Indomethacin (10(-4) M) was a considerably more potent inhibitor of HCO-3 secretion than of H+ secretion in the fundus and also inhibited HCO-3 transport in the antrum. Fenclofenac (3 x 10(-3) M) almost abolished fundic HCO-3 transport and also depressed H+ secretion. There was a marked fall in transmucosal potential difference and a decrease in electrical resistance in fenclofenac-treated mucosae whereas indomethacin had less effect on electrical properties at the concentrations used here. The prostaglandins, E2, 16,16-dimethyl E2 and I2 all inhibited H+ secretion but only 16,16-dimethyl E2 stimulated HCO-3 secretion. The inhibitory action of indomethacin on HCO-3 secretion was prevented by co-administration of 16,16-dimethyl PGE2 (10(-6) M). It is proposed that the inhibitory action of nonsteroidal antiinflammatory drugs and the stimulatory action of some prostaglandins on HCO-3 secretion contributes to their ulcerogenic and anti-ulcer actions on the gastric mucosa.

Animals↗
PubMed1978

Gastric HCO3--secretion in the guinea pig.

Measurement of gastric intraluminal PCO2 and pH in the anesthetized guinea pig enabled simultaneous determination of total H+ and HCO3- gastric secretions. There was quantitative agreement between the release of CO2 and decrease in HCO3- after intragastric instillation of HCl. The basal rate of HCO3- secretion (approximately 40 mueq-h-1) was, in most cases, smaller than spontaneous H+ secretion, but gastric net secretory output was alkaline (HCO3- greater than H+) after inhibition of acid secretion with histamine H2-receptor antagonists (cimetidine 20 mg-kg-1 or metiamide 35 mg-kg-1). Carbachol (1-2 microgram-kg-1) stimulated secretion of both HCO3- and H+; only the latter response was sensitive to the histamine antagonists. Atropin (100 microgram-kg-1) blocked stimulation of HCO3- secretion but did not affect the basal output of HCO3-. An increase in HCO3- secretion was associated with an equivalent increase in net Na+ influx and an increase in the net influx of Cl- with H+ plus K+. Intragastric neutralization of H+ by HCO3- is likely to occur at the mucosal surface and may protect the mucosa from the damaging effects of intraluminal acid.

Acid-Base Equilibrium↗
PubMed1977

Active alkalinization by amphibian gastric fundic mucosa in vitro.

Gastric fundic mucosae in vitro from four species of frog and Necturus secrete HCO-3 at a steady-state rate of 0.25-0.55 microneq-cm-2-h-1 which corresponds to 5-10% of maximal H+ secretion. Net alkalinization was quantitated in mucosae with spontaneously resting H+ secretion or in mucosae inhibited by histamine H2-receptor antagonists or SNC-. HCO-3 secretion was inhibited by DNP (10(-4) M), CN- (10(-2) M), or anoxia. Acetazolamide inhibited alkalinization at 10(-2) M when added to the nutrient side and at 10(-4) M on the luminal side. Carbachol (10(-4) M) and DBcGMP (10(-4) M) stimulated alkalinization and caused a transient rise in the transmucosal PD; DBcAMP (10(-3) M) was without effect. An almost identical secretion occurred spontaneously in antral mucosae and was insensitive to histamine (10(-5) M). Occurrence in both antral and fundic mucosa suggests that active alkalinization is a property of gastric surface epithelial cells. Gastric alkalinization may protect the luminal surface of the mucosa from the damaging effects of acid and contribute to the continuous removal of H+ ions from gastric contents.

Acetazolamide↗
PubMed1976

Passive cutaneous anaphylaxis in guinea pigs elicited by gastric absorption of dextran induced by acetylsalicylic acid.

Passive cutaneous anaphylaxis (PCA) was elicited in guinea pigs sensitized with rabbit antidextran by the absorption of dextran macromolecules from the stomach induced by intragastric acetylsalicylic acid. The gastric contents had a pH sufficiently low to maintain the acid mainly in the unionized form since it is the latter which alters gastric permeability. The acid concentration required to induce PCA was below that which caused mucosal cell loss or bleeding. The maximal molecular weight of the absorbed dextran was approximately 25,000. Dextran was chosen as antigen because of its well-characterized physical and immunological properties. It is suggested that ingestion of acetylsalicylic acid may contribute to sensitization and allergic reactions to antigenic food materials by facilitating their absorption from the stomach.

Absorption↗
PubMed1975

Ion transport by amphibian antrum in vitro. I. General characteristics.

Both Necturus and bullfrog antrum show stable PD, resistance, and short-circuit current (Isc) when mounted in an Ussing chamber. Measurements of Na+ and Cl minus flux showed that both ions are actively transported across Necturus antrum, Na+ from secretory to nutrient, Cl minus from nutrient to secretory (both net fluxes being similar to 0.30 mueq cm minus 2 h minus 1). Only the Na+ transport contributed to the Isc and PD as evidenced by a) Na+ removal, b) the effects of amiloride on the secretory surface, c) the effects of ouabain on the nutrient side. Microelectrode experiments confirm the Na+ conductance of the secretory cell membrance, a HCO3 minus conductance of both cell membranes, and a KCl conductance across the nutrient cell membrane. In addition, antrum apparently secretes alkali (similar to 0.35 mueq cm minus 2 h minus 1), which secretion is sensitive to metabolic inhibitors and Diamox. Nutrientside HCO3 minus increased the rate of alkaline secretion and a transmucosal HCO3 minus gradient could contribute to ISC and PD. A model is proposed to account for the electrical properties of the tissue.

Amiloride↗
PubMed1975

Distribution of intravenous sodium acetylsalicylate in the unanaesthetized rat on stimulation and inhibition of gastric secretion.

Sodium carboxyl-14C acetylsalicylate was injected intravenously into fasted rats in which gastric secretion was either inhibited by atropine or stimulated by histamine. After one hour blood samples and specimens from the glandular portion of the gastric mucosa, muscle, liver, and kidney were taken. The 14C activity in the blood and specimens was determined by liquid scintillation counting after combustion. The drug concentration was lowest in muscle and gastric mucosa, intermediate in the liver, and highest in the kidney, where it equalled that in the blood. The concentrations were proportional to the amount of drug injected in all the examined tissues. There was no difference between rats given histamine and those given atropine. The secretory state of the gastric mucosa thus did not affect the concentration of the drug in this tissue when acetylsalicylate was given intravenously.

Animals↗