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Biomedical subjects

K F Sewing

Publications and source records attributed to K F Sewing.

At least 163 records · Page 9Linked to original sources
PubMed1985

Binding of 3H-iloprost to rat gastric mucosa: a pitfall in performing radioligand binding assays.

Binding of 3H-iloprost was studied in a 20,000 x g sediment of the rat gastric mucosa. When pH in both test tubes for total and non-specific binding was kept identical, no displaceable binding of iloprost could be detected. When no care was taken to keep the pH identical in corresponding test tubes of the binding assay, changes in pH simulated specific and displaceable binding of iloprost. Therefore it is concluded that - in contrast to earlier reports - it is not possible to demonstrate specific iloprost binding using the given method.

Animals↗
PubMed1985

Localization of indomethacin induced inhibition of oxygen consumption in mitochondria of the guinea pig gastric mucosa.

The effect of indometacin-Na-trihydrate on oxygen consumption was studied in isolated mitochondria of the guinea pig gastric mucosa. Using various substrates with or without inhibitors it was possible to localize the inhibitory effect on or in the vicinity of complexes I and III of the respiratory chain. Effective concentrations of indometacin were within the range of gastric mucosal concentrations reached with submaximal ulcerogenic doses.

Animals↗
PubMed1984

Inhibition of partially purified K+/H+-ATPase from guinea-pig isolated and enriched parietal cells by substituted benzimidazoles.

The cellular and subcellular distributions of adenosinetriphosphatases (ATPases) were examined in guinea-pig gastric mucosal cells. All cell types displayed Mg2+-ATPase and bicarbonate (HCO3-)-stimulated ATPase activity. K+-ATPase was located only in fractions derived from parietal cells. Differential and density-gradient centrifugation of material prepared from parietal cells revealed that K+-ATPase activity was located in a tubulo-vesicular membrane fraction. Enzyme activity was ten fold greater in this fraction than in a crude parietal cell homogenate. The substituted benzimidazoles, omeprazole and picoprazole, inhibited K+-ATPase (IC50 1.8 +/- 0.5 mumol l-1 and 3.1 +/- 0.4 mumol l-1, respectively). Detailed kinetic analysis indicated that these compounds were non-competitive and reversible inhibitors of the enzyme. In contrast cimetidine and verapamil were without effect on the enzyme. The relevance of the inhibition of K+-ATPase to the antisecretory activity of the benzimidazoles, in experimental animals and man, is discussed.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1984

Effect of oral 16,16-dimethyl prostaglandin E2 on gastric mucosal salicylate concentration in the rat.

The effect of 16,16-dimethyl prostaglandin E2 (DmPGE2), in doses subthreshold for antisecretory activity, were examined in female rats. The aims were to determine if DmPGE2 alters the disposition of acetylsalicylic acid (ASA) within the gastric mucosa and if DmPGE2 could attenuate the ulcerogenic effect of oral ASA. Gastric lesions occurred after an oral, but not an intravenous dose of 150 mg/kg ASA. Lesions could be prevented by pretreatment with 5 micrograms/kg DmPGE2 orally 30 min prior to ASA. DmPGE2 elevated fundic concentrations of both ASA and salicylic acid (SA) within the first hour when ASA was given orally. The ratio of the concentration of ASA/SA in fundus was not changed, indicating that DmPGE2 did not depress the fundic esterase activity. It is concluded that the cytoprotective effect of DmPGE2 is not related to a change in mucosal concentration or elimination of ASA or SA.

Administration, Oral↗
PubMed1983

Effect of substituted benzimidazoles on acid secretion in isolated and enriched guinea pig parietal cells.

The inhibitory effect of the three benzimidazole derivatives timoprazole, picoprazole, and omeprazole on histamine and dbcAMP stimulated 14C-aminopyrine accumulation (= H+ secretion) has been studied in isolated and enriched guinea-pig parietal cells. All compounds tested inhibited H+ secretion in a concentration dependent manner with IC50 values of 8.5 +/- 1.9 mumol/l for timoprazole, 3.9 +/- 0.7 mumol/l for picoprazole, and 0.13 +/- 0.03 mumol/l for omeprazole. The IC50 of timoprazole, when dbcAMP was used as a stimulus, did not differ significantly from that of histamine stimulation. The type of inhibition was of a non-competitive nature. The full acid response to histamine after temporary exposure of the cells to the benzimidazoles could be restored by washing the cells twice; this suggests that the inhibition is reversible. The data - among others - indicate that the properties of the benzimidazoles described here would allow these compounds to be used as effective antisecretagogues.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1983

Calcium channel antagonists verapamil and gallopamil are powerful inhibitors of acid secretion in isolated and enriched guinea pig parietal cells.

In isolated and enriched guinea pig parietal cells the inhibitory effects of the calcium channel antagonists verapamil and gallopamil on 14C-aminopyrine uptake (= H+ secretion) have been analyzed. Both verapamil and gallopamil inhibit acid secretion in a concentration-dependent manner with an IC50 of 12.1 and 10.9 mumol/l respectively. The type of inhibition is noncompetitive in nature. Verapamil inhibits the acid response to histamine, dibutyryl-cAMP, and KCl with IC50 values not significantly different from each other. Exposure of the cells to verapamil and subsequent washing enhances the acid response to histamine for an unknown reason. It is concluded that the calcium channel antagonists verapamil and gallopamil inhibit acid secretion in vitro by interfering with the parietal cell proton pump, the K+/H+-ATPase.

Adenosine Triphosphatases↗
PubMed1982

Comment: effects and side effects of H1- and H2-receptor antagonists in clinical situations.

The combined administration of H1- and H2-receptor antagonists has been shown to be beneficial in clinical situations in which the release of histamine causes trouble. It needs to be shown whether the use of either type of histamine antagonists would be as effective as the combination. Side effects of H1- and H2-receptor antagonists are mild and can be controlled. The various reports during this symposium have shown that most of the drugs which can release histamine have been replaced by other drugs not having this property. That seems to be more effective to cope with histamine than to try to antagonize the effects of endogenously released histamine. Let us call it the zero-option.

Histamine H1 Antagonists↗
PubMed1981

Histamine uptake and metabolism in intact isolated parietal cells.

3H-Histamine binding, uptake and metabolism were investigated in intact isolated and enriched parietal cells from the dog and guinea pig. Histamine uptake was sodium dependent and followed by intracellular metabolism. The only metabolite that was detected and extracted from cytosol has been identified by TLC to N tau-methylhistamine. The histamine N-methyltransferase activity appeared to be sodium dependent and was inhibited by mepyramine and chlorpromazine, and also by higher concentrations (10(-4)--10(-3) mol/l) of cimetidine. Two blockers of the sodium channel, amiloride an aminoguanidine, also reduced the enzyme activity by an as yet unknown mechanism.

Amiloride↗
PubMed1981

Adrenaline sensitive adenylate cyclase in human gastric mucosa.

Basal and adrenaline-stimulated adenylate cyclase (AC) was studied in biopsy specimens of the gastric and duodenal mucosa from 112 individuals. AC activities were log normally distributed. AC of fundic and antral gastric mucosa responded to adrenaline in a concentration-dependent manner, that of the duodenal mucosa did not respond to adrenaline. The degree of activation in biopsies of normal gastric mucosa was similar to that of patients with chronic atrophic gastritis or patients antrectomized according to the Billroth method. AC in biopsies from cimetidine-treated peptic ulcer patients was less sensitive to adrenaline than AC in biopsies from untreated patients. The threshold concentration of cimetidine to inhibit adrenaline-stimulated AC in vitro was 10(-6) mol/l. The data provide evidence of an adrenaline-sensitive AC in cells other than parietal cells and show an inhibitory action of cimetidine on the catecholamine-sensitive AC in the human gastric mucosa.

Adenylyl Cyclases↗
PubMed1981

Comparative study with ranitidine and cimetidine on gastric secretion.

The inihibitory effect of various doses of ranitidine and cimetidine on pentagastrin stimulated volume, acid, and pepsin secretion was studied in 8 healthy volunteers. Both compounds inhibited all three variables in a dose dependent manner with an average ID50 of approximately 5 mg for ranitidine and of approximately 41 mg for cimetidine. On a molar basis ranitidine is about 11 times more potent than cimetidine. The duration of action of both compounds appears to be equally long.

Adult↗
PubMed1980

Binding studies with 3H-atropine in intact isolated guinea pig gastric mucosal cells.

3H-atropine binding was studied in isolated intact guinea pig gastric mucosal cells and has been shown to be saturable. Scatchard plots of the binding system calculated under the assumption of only one binding site revealed KD values for the parietal cell enriched population of 1.25 x 10(-6) mol/l and 1.38 x 10(-6) mol/l for the nonparietal cells. The results show that in gastric mucosa both parietal and nonparietal cells contain cholinergic receptors.

Animals↗