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Biomedical subjects

W Schepp

Publications and source records attributed to W Schepp.

105 records · Page 6Linked to original sources
PubMed1985

Effects of hormones (calcitonin, GIP) and pharmacological antagonists (ranitidine and famotidine) on isolated rat parietal cells.

The rationale for the present study was to compare calcitonin and gastric inhibitory polypeptide (GIP) versus two histamine H2 receptor antagonists with respect to their potency of inhibiting parietal cell functions. Adenylate cyclase activity and acid production ([14C]aminopyrine uptake) of isolated rat parietal cells were stimulated by histamine. At 10(-7) and 10(-6) mol/l, calcitonin and GIP reduced the response to histamine by 10-20% following noncompetitive kinetics. Ranitidine and famotidine (MK 208) inhibited the response to histamine by about 50% at 10(-7)-10(-6) mol/l, and at 10(-5) mol/l abolished the histamine effect. On a molar basis famotidine turned out to be 6 times more potent than ranitidine. Both antagonists revealed competitive kinetics. Our data suggest direct inhibition of the parietal cells by the tested compounds which were shown to interfere at the adenylate cyclase cAMP system or at the histamine H2 receptor. However, compared to the histamine H2 receptor antagonists, hormonal inhibition is less pronounced and mediated by a different mechanism.

Adenylyl Cyclases↗
PubMed1985

H+ production by isolated cells from human gastric mucosa.

Gastric mucosal cells were isolated from human mucosa obtained at surgery. H+ production was indirectly estimated by 14C aminopyrine (AP) uptake. The maximal response to histamine occurred after 30 min of incubation whereas intrinsic factor (IF) secretion was maximal after only 7.5 to 15 min. According to the concentration response curve 10(-4) mol/1 histamine proved to be the most effective concentration, the response to which was completely inhibited by ranitidine. Carbachol, dibutyryl cAMP and IMX also enhanced AP uptake, IMX being even more powerful than histamine. Carbachol and IMX failed to potentiate the response to histamine. Parietal cell fractions enriched by a Percoll density gradient revealed a pronounced background stimulation so that additional stimulation by test agents was less effective than in non-fractionized cells.

Adult↗
PubMed1985

Histamine content and release of isolated rat gastric mucosal cells.

Enzymatically dispersed rat gastric cells were subdivided (Percoll) in fractions (F1, F2, F3) with different number of parietal cells (PC) and the intracellular histamine content was estimated (ng/10(6) cells): F1 (9% PC): 17 +/- 4 (SEM), F2 (26% PC): 80 +/- 9 and F3 (77% PC): 134 +/- 15. Histidinedecarboxylase showed the same pattern of distribution, F1 low, F2 medium, F3 high activity. Incubated F3 cells constantly released histamine (19 +/- 3 ng/10(6) cells/h), a process which could be stimulated by carbachol, forskolin and hexoprenaline. The data suggest: rat gastric histaminocytes copurify with PC, background stimulation by histamine should be considered in isolated cell systems, vagal stimulation may release histamine within the gastric mucosa.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Intrinsic factor secretion from isolated human gastric mucosal cells.

Human gastric mucosal cells were isolated from the resected fundic mucosa of peptic ulcer patients. The intracellular content and secretion of intrinsic factor were estimated by binding to cyano[57Co]cobalamin. The content was maximal in the enriched parietal cell fraction which also displayed the highest H+ production as measured by amino[14C] pyrine uptake. Secretagogues evoked full response after 15 min of incubation: pentagastrin (181% of basal secretion), carbachol (208%), histamine (250%) and dibutyryl cyclic adenosine monophosphate (304%). The phosphodiesterase inhibitor isobutylmethylxanthine was slightly more effective even than dibutyryl cAMP. The response to histamine was abolished by ranitidine, indicating activation of adenylate cyclase via histamine H2 receptors, but remained unaffected by atropine, which in turn blocked the carbachol effect, whereas ranitidine was ineffective. The mean formation rate was 8.4 fmol intrinsic factor/10(6) cells per h under basal conditions and 14.3 fmol in response to histamine.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Adenylate cyclase and H+ production of isolated rat parietal cells in response to glucagon and histamine.

The effect of glucagon and its interaction with histamine on adenylate cyclase (AC), cellular cAMP and [14C]aminopyrine ( [14C]AP) uptake, a reliable index of parietal cell H+ production, was studied in isolated rat gastric cells. AC activation in response to glucagon and histamine correlated with the number of parietal cells. Glucagon (10(-10)-10(-6) mol/l) increasingly stimulated AC (maximal effect: 92% by 10(-7) mol/l) and cellular cAMP (86% by 10(-9) mol/l) of fractions enriched with 80% parietal cells but did not cause a pronounced change of the histamine-stimulated enzyme. If there was any interaction, the effect of both hormones was additive. Glucagon neither changed basal [14C]AP uptake nor interfered with that in response to histamine. The data suggest that if glucagon activates a parietal cell AC this process is not followed by parietal cell H+ production. Furthermore, unlike other inhibitors such as somatostatin or PGE2, glucagon does not reduce acid secretion via the cAMP system of the parietal cell.

Adenylyl Cyclases↗
PubMed1984

Intrinsic factor secretion from isolated gastric mucosal cells of rat and man--two different patterns of secretagogue control.

Intrinsic Factor (IF) secretion was studied using isolated gastric mucosal cells from rat and man. In the rat, IF was localized to the chief cells and its secretion responded most efficaciously to carbachol. DbcAMP and hexoprenaline were less powerful, whereas histamine and pentagastrin lacked any effect. In man, IF secretion derived from the parietal cells and was increasingly enhanced by hexoprenaline, pentagastrin, carbachol, histamine and dbcAMP. In both species, IF secretion differs with respect to its cellular origin and the pattern of secretagogue control: IF release from rat chief cells is due to muscarinic receptor excitation, whereas IF release from human parietal cells responds predominantly to histamine-H2-receptor activation and seems to be mediated by the cAMP system.

Adenylyl Cyclases↗
PubMed1983

Cellular origin and release of intrinsic factor from isolated rat gastric mucosal cells.

The cellular content and secretion of intrinsic factor was measured by [57Co]cyanocobalamin binding using isolated rat gastric mucosal cells. The intrinsic factor/R-protein ratio was above 9:1 as evaluated by specific anti-intrinsic factor antibodies. In unfractionized cells with 23 +/- 1.3% parietal cells the intrinsic factor content of 148 +/- 47 fmol/10(6) cells remained almost unchanged over 3 h, whereas basal secretion rose up to 57 +/- 10. In fractionized cells (Percoll) with 3-85% parietal cells most intrinsic factor was found in the parietal cell-depleted fraction (content: 441 +/- 30, secretion/3 h: 139 +/- 16, mean formation/h: 50 +/- 12 fmol/10(6) cells). The intrinsic factor content of the different cell fractions correlated with that of pepsin. [14C]Aminopyrine uptake, an indirect measure of parietal cell H+ production, was inversely related. Carbachol (1 X 10(-6)-10(-3) mol/l) stimulated intrinsic factor secretion, 1 X 10(-3) mol/l being maximally effective (90 +/- 8% above basal). This response was inhibited by atropine and pirenzepine, but not by prostaglandin E2 (PGE2) and somatostatin. Dibutyryl cyclic adenosine monophosphate (dibutyryl cAMP, 43 +/- 7%) and hexoprenaline (24 +/- 5%) enhanced intrinsic factor secretion less effectively and pentagastrin like histamine lacked any stimulatory effect. We conclude that in the rat intrinsic factor is produced and released from chief cells mainly under cholinergic control.

Aminopyrine↗
PubMed1983

Comparison of the effect of PGE2 and somatostatin on histamine stimulated 14C-aminopyrine uptake and cyclic AMP formation in isolated rat gastric mucosal cells.

In isolated rat gastric cells somatostatin and PGE2 were compared in respect to their effects on the cAMP system and on the histamine-stimulated H+-production, measured by 14C-aminopyrine (14C-AP) uptake. Like PGE2 somatostatin activated adenylate cyclase (AC) for all in non-parietal cells. This effect on AC declined in cell fractions with increasing number of parietal cells. Activation of AC or elevation of cellular cAMP and uptake of 14C-AP in response to histamine were inhibited by 10(-9) to 10(-5) mol/1 PGE2 and somatostatin. The results indicate remarkable similarity between somatostatin and PGE2: both activate a non-parietal cell AC and both inhibit H+-production, likely by interfering at the histamine sensitive AC of the parietal cell.

Adenylyl Cyclases↗
PubMed1983

Aminopyrine accumulation of isolated parietal cells from the rat stomach. Effect of histamine and interaction with endogenous inhibitors.

The inhibitory properties of secretin, vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), somatostatin and prostaglandin E2 (PGE2) on acid production in response to histamine were tested in vitro by measuring the 14C-aminopyrine (14C-AP) uptake into isolated rat parietal cells, a reliable index of H+ generation. All compounds significantly inhibited 14C-AP accumulation and 4 X 10(-8) mol/l secretin, 7 X 10(-8) mol/l PGE2 and 2 X 10(-7) mol/l CCK decreased the effect of 10(-4) mol/l histamine by 50% (IC50). VIP and somatostatin did not reduce AP-uptake to such extent and the approximate IC50 values could not be established. The type of inhibition by all peptides and PGE2 appeared not to be competitive in nature. Our data suggest that these compounds inhibit acid production by a mechanism localized directly at the parietal cell and that secretin and CCK are unlikely to exert a physiological role as inhibitors of gastric acid secretion.

Aminopyrine↗
PubMed1980

No influence of age and gastric acid secretion on serum vitamin B12 concentration.

Serum vitamin B12 concentration, parietal cell antibodies (PCA), peak acid output vitamin B12 resorption capacity were determined in 76 patients (age 23 to 82 years). Gastroscopy was performed on all of these patients; guided biopsy was taken from 70 of them. No influence of the inflammatory changes in the gastric mucosa, sex or the presence of PCA on the serum vitamin B12 concentration were demonstrable in our patients, who all revealed a vitamin B12 resorption in the normal range. In particular we were unable to confirm the observation of Döscherholmen et al. (5) of a fall in serum vitamin B12 concentration with increasing age or decreasing PAO. Hence the estimation of the serum vitamin B12 concentration cannot be used as a screening test for selecting those patients suffering from chronic atrophic gastritis and achlorhydria, who should be monitored by gastroscopy and biopsy because of an increased risk of gastric cancer.

Achlorhydria↗
PubMedDate not supplied

Naturally occurring opioid peptides modulate H+-production by isolated rat parietal cells.

The rationale for the present study was to determine the effects of naturally occurring opioid peptides on H+-production by isolated rat parietal cells as indirectly measured by [14C]-aminopyrine uptake. In crude preparations (18 to 25% parietal cells) and in enriched (80 to 90%) parietal cell fractions stimulation by submaximal histamine- or dibutyryl cAMP-concentrations (10(-6)-10(-4) mol/l) was augmented by 20-30% in the presence of methionine-enkephalin (Met-Enk) and Met-Enk Arg6Phe7 (10(-7) to 10(-5) mol/l). This augmentation was blocked by the opiate receptor antagonist (-)naloxone (10(-6) mol/l) suggesting specificity of the action of Met-Enk and Met-Enk Arg6Phe7. At 10(-6) mol/l (-)naloxone did not exert nonspecific toxic effects. Yet, even in the absence of exogenous opioids, histamine-induced H+-production was inhibited by 3 X 10(-5) or 10(-4) mol/l (-)naloxone. Since similar inhibition occurred with (+)naloxone, an inactive stereoisomer which does not interact with opiate receptors, effects of (-)naloxone at concentrations above 10(-5) mol/l must be considered nonspecific. We conclude that Met-Enk and Met-Enk Arg6Phe7 have no effect on basal, but augment stimulated H+-production by a direct effect on the parietal cells. At nontoxic concentrations (-)naloxone antagonizes this augmentation indicating that it is mediated by specific opiate receptors on the parietal cells.

Aminopyrine↗
PubMedDate not supplied

Biotinylation of a bombesin/gastrin-releasing peptide analogue for use as a receptor probe.

The development of a biotinylated bombesin/gastrin-releasing peptide (GRP) for use as a receptor probe is reported. The lysine13 of a GRP-27 was substituted by arginine and lysine was added to the amino terminus. Biotinylation of the N-terminal lysine was performed. The biotinylated peptide was purified by HPLC and characterized by mass spectral analysis. Binding studies with murine Swiss 3T3 fibroblasts, cells known to express bombesin/GRP receptors, yielded a dissociation curve for the biotinylated GRP-27 analogue (biotin-Lysyl[Asp12,Arg13]GRP-27) which was nearly identical to that of native GRP. Using studies of gastrin release from isolated canine G cells, equipotent functional activity of the biotinylated probe and unmodified GRP was demonstrated. Measurements of retained 125I-avidin confirmed that the biotin/avidin interaction could occur once the biotin-peptide complex was bound. Applicability of the probe was demonstrated with fluorescent microscopy using avidin-FITC on Swiss 3T3 fibroblasts. In conclusion, a novel biotinylated bombesin/GRP analogue has been developed which retains the functional characteristics of the native peptide and is a useful probe for receptor studies.

Amino Acid Sequence↗
PubMedDate not supplied

Oxyntomodulin: a cAMP-dependent stimulus of rat parietal cell function via the receptor for glucagon-like peptide-1 (7-36)NH2.

We have previously shown that in highly enriched rat gastric parietal cells the intestinal peptide hormones oxyntomodulin and glucagon-like peptide-2 (GLP-2) compete for receptor-binding with glucagon-like peptide-1 (GLP-1), a potent cAMP-dependent stimulus of H+ production in vitro. It is, however, unknown whether oxyntomodulin and GLP-2 elicit a biological response by interacting with the GLP-1 receptor. Therefore, we used enriched rat parietal cells to investigate the effects of both hormones on the production of cAMP and H+ ([14C]aminopyrine accumulation). Both parameters were stimulated by oxyntomodulin in a concentration-dependent manner. EC50 values were 6.2.10(-8) and 2.5.10(-7) M oxyntomodulin for stimulation of H+ and cAMP production, respectively. The maximally effective concentrations for stimulation of [14C]aminopyrine accumulation and cAMP production were 1.10(-6) and 1.10(-5) M oxyntomodulin, respectively. At these concentrations oxyntomodulin was nearly as effective as 10(-4) M histamine and equally effective as 10(-8) M GLP-1 (7-36)NH2. In the enriched parietal cell preparation there was no immunocytochemical evidence of contaminating D cells. Accordingly, the responses to oxyntomodulin and GLP-1 (7-36)NH2 were not augmented by incubating the cells in the presence of a polyclonal anti-somatostatin antibody. [14C]Aminopyrine accumulation in response to oxyntomodulin was inhibited by the GLP-1 (7-36)NH2 receptor antagonist, exendin (9-39)NH2, but not by the H2-receptor antagonist, ranitidine. Oxyntomodulin and carbachol acted additively to stimulate [14C]aminopyrine accumulation. GLP-2 (10(-7) to 10(-5)M) was without effect on basal H+ and cAMP production; however, at 10(-5) M GLP-2 markedly inhibited oxyntomodulin-stimulated [14C]aminopyrine accumulation. It is concluded that, by interacting with parietal cell receptors for GLP-1 (7-36)NH2, oxyntomodulin, but not GLP-2, directly stimulates H+ production by activating the adenylate cyclase.

Aminopyrine↗
PubMedDate not supplied

Proton pump inhibitory therapy: then and now.

Proton pump inhibitors (PPIs) have been established as the new "gold standard" for traditional acid-inhibitory treatment of the so called "peptic" diseases. Due to the high antisecretory and ulcer-healing potency of omeprazole, no major improvements of the efficacy in ulcer healing and pain relief can be expected. Pantoprazole, as a further development in PPIs, is characterized by improved pharmacokinetic behavior as well as by higher tissue selectivity and binding specificity and by a very low potential to interact with the cytochrome P450 enzyme system. These characteristics may provide the basis for a low potential for side effects and for a more favorable interaction profile, although the clinical relevance of these potential advantages remains to be proven. Reflux esophagitis will also remain a domain for the traditional use of PPIs in the future. However, in the treatment of gastroduodenal ulcers, the acid inhibitory potential of PPIs will be used mainly to facilitate the eradication of H. pylori.

Anti-Bacterial Agents↗