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C Prinz

Publications and source records attributed to C Prinz.

At least 37 records · Page 2Linked to original sources
PubMed1998

Identification and functional importance of IL-1 receptors on rat parietal cells.

We studied the expression of interleukin-1 (IL-1) receptors and the effect of IL-1beta on the function of highly enriched (>97%) rat parietal cells. RT-PCR of parietal cell poly(A)+ RNA with primers specific for the rat IL-1 receptor revealed a single 547-kb PCR product highly homologous to the published sequence of the IL-1 receptor. Northern blot analysis of poly(A)+ RNA of rat parietal cells and brain revealed a single RNA species of 5.7 kb. Cytochemistry of parietal cell IL-1 receptor was performed with biotinylated recombinant human IL-1beta, visualized by avidin-coupled fluorescein. Corresponding to the high degree of parietal cell enrichment, 95% of the cells stained positive. Basal H+ production ([14C]aminopyrine accumulation) was not changed by IL-1beta (0.25-100 pg/ml) nor was the response to histamine or carbachol when added simultaneously with the cytokine. However, when parietal cells were preincubated with IL-1beta (0.5-5 pg/ml) for 10 min before the addition of histamine or carbachol, the response to these secretagogues was reduced by 35 and 67%, respectively. Inhibition by IL-1beta was fully reversed by the human recombinant IL-1 receptor antagonist. Preincubation of parietal cells with IL-1beta failed to alter histamine-stimulated cAMP production but markedly inhibited carbachol-induced formation of D-myo-inositol 1,4, 5-trisphosphate. In fura 2-loaded, purified parietal cells, 10 min preincubation with IL-1beta dramatically reduced the initial transient peak elevation of intracellular Ca2+ concentration in response to carbachol. We conclude that rat parietal cells express IL-1 receptors mediating inhibition of H+ production. The antisecretory effect of IL-1beta may contribute to hypoacidity secondary to acute Helicobacter pylori infection or during chronic colonization by H. pylori preferring the fundic mucosa.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Growth factor effects on apoptosis of rat gastric enterochromaffin-like cells.

Enterochromaffin-like (ECL) cells are histamine-containing endocrine cells in the gastric epithelium that show increased density during chronic atrophic gastritis. The current study determined cell number and apoptosis of isolated rat ECL cells in response to several growth factors. Isolated ECL cells from fundic mucosa (enrichment >90%) were grown in serum-free medium over 2-5 days. Cell number was determined by mitochondrial formazan production; apoptosis was measured by Tdt-mediated dUTP nick end labeling reaction and DNA fragmentation-based enzyme-linked immunosorbent assay. Immunocytochemistry and RT-PCR demonstrated the presence of epidermal growth factor receptor, neuronal growth factor receptor (type 1), and fibroblast growth factor (FGF) receptor (type 1). Gastrin (EC50, approximately 2 pM), transforming growth factor-alpha (TGF alpha; 10-30 ng/ml), and basic FGF (bFGF; 1-10 ng/ml) increased the total number of cultured ECL cells. bFGF augmented the gastrin (1 pM)-induced response. Beta-neuronal growth factor (10 ng/ml) and bFGF (2 ng/ml) decreased the programed death of ECL cells. Interleukin-1beta (100 pg/ml, 24 h) stimulated apoptosis 2- to 3-fold in ECL cells, and simultaneous incubation with TGF alpha (20 ng/ml) or bFGF (2 ng/ml) significantly inhibited this effect. ECL cells express specific receptors for gastrin, epidermal growth factor, neuronal growth factor, and FGF. bFGF prolonged ECL cell survival by inhibiting spontaneous apoptosis. Our data further indicate that TGF alpha and bFGF increase ECL cell number by inhibiting cytokine-induced programed cell death.

Animals↗
PubMed1997

Functional impairment of rat enterochromaffin-like cells by interleukin 1 beta.

BACKGROUND & AIMS: Histamine-producing enterochromaffin-like (ECL) cells play an integrative role in the regulation of acid secretion. Decreased mucosal histamine concentrations and increased levels of interleukin (IL) 1 beta, IL-6, and IL-8 have been detected in the gastric mucosa inflamed with Helicobacter pylori. The aim of this study was to investigate the response of isolated ECL cells to these cytokines. METHODS: Enriched rat gastric ECL cells (85%-95%) were cultured for 2-4 days. RESULTS: Polymerase chain reaction showed IL-1 and IL-6, but not IL-8 receptors, in ECL cell complementary DNA. Positive receptor staining with biotinylated IL-1 beta corresponded to ECL cell enrichment (92%). IL-6 and IL-8 had no effect on histamine secretion. IL-1 beta (2 U/mL) stimulated basal histamine secretion and nitric oxide production within 60 minutes and cyclic guanosine monophosphate production within 20 minutes. Pretreatment for 20 minutes with IL-1 beta (2 U/mL) attenuated gastrin-stimulated histamine secretion by 40%-50%, reversed by the IL-1 receptor antagonist (10 U/ mL). Pretreatment for 20 minutes with IL-1 beta (2 U/mL) completely inhibited gastrin-stimulated (1 nmol/L) histidine decarboxylase activity. IL-1 beta (2 U/mL, 60 minutes) increased lactate dehydrogenase release to 25% of cell content. Cells pretreated with IL-1 beta did not respond to gastrin after a further 48-hour culture and showed decreased histamine content. CONCLUSIONS: ECL cells appear to express IL-1 receptors. IL-1 beta causes sustained functional impairment of ECL cells in vitro.

Animals↗
PubMed1997

Physiology of isolated gastric endocrine cells.

The regulation of gastric acid secretion is achieved in the periphery by interplay between three major gastric endocrine cells: the enterochromaffin-like (ECL) cell, the gastrin or G cell, and the somatostatin or D cell. Regulation of these cells is via stimulatory or inhibitory paracrine, endocrine, and neural pathways. Upregulation of ECL function is determined by activation of CCK-B receptors, by gastrin, and by activation of beta-adrenergic receptors, as well as by acetylcholine in some (10-29%) of the cells. Gastrin and acetylcholine produce typical biphasic calcium signals. Inhibition of ECL cell histamine release and calcium signaling is produced by somatostatin acting at a type 2 receptor, histamine acting at a histamine-3 receptor, and by peptide PYY. Stimulation of ECL cells results in activation of chloride channels, and there is evidence that voltage-dependent calcium channels, along with the receptor-operated calcium channels, also are responsible for elevation of [Ca]i. Depolarization-activated K+ channels presumably restore the potential after depolarization by activation of the chloride channel. The D cell is activated by either gastrin or CCK and appears to be inhibited by acetylcholine and somatostatin. The G cell is activated by acetylcholine and gastrin-releasing peptide (GRP) and is inhibited by somatostatin. The functional integration of these three cell types is the primary determinant of the degree of stimulation of the parietal cell.

Animals↗
PubMed1997

Functional importance of synaptobrevin and SNAP-25 during exocytosis of histamine by rat gastric enterochromaffin-like cells.

Gastric enterochromaffin-like (ECL) cells release histamine upon stimulation with gastrin in a calcium-dependent manner. The intracellular mechanisms and proteins mediating exocytosis of histamine-containing vesicles in ECL cells have not been determined yet. We used immunocytochemistry to show the localization of SNAP-25 (synaptosome-associated protein of 25 kDa) and synaptobrevin VAMP (vesicle-associated membrane protein) in ECL cells of the rat gastric mucosa and in isolated, highly enriched ECL cells, which were identified with an antibody directed against the marker enzyme histidine decarboxylase. Immunoblots of isolated ECL cells demonstrated the presence of SNAP-25, synaptobrevin, synaptophysin, synaptotagmin, and syntaxin. Histamine release from isolated ECL cells permeabilized with 8 microM digitonin (2 min) was stimulated approximately 2.5-fold upon exposure to calcium (30 microM; 10-min incubation). Preincubation with 1 microM tetanus toxin light chain for 15 min attenuated calcium-induced histamine release by 40-50% and almost completely cleaved synaptobrevin. Botulinum neurotoxin A (100 nM) totally blocked calcium-induced histamine release and cleaved SNAP-25. We conclude that synaptobrevin, synaptophysin, synaptotagmin, SNAP-25, and syntaxin are present in gastric ECL cells. Inhibition of histamine secretion by clostridial neurotoxins associated with the cleavage of synaptobrevin and SNAP-25 implicates the functional importance of these proteins in the docking and fusion of histamine vesicles.

Animals↗
PubMed1996

Potassium and chloride currents in rat gastric enterochromaffin-like cells.

The gastric enterochromaffin-like (ECL) cell secretes histamine in response to secretagogues (gastrin, acetylcholine) by calcium signaling-dependent exocytosis of intracellular vacuoles containing the hormone. ECL cells were isolated from rat fundic gastric mucosa by elutriation and density-gradient centrifugation. Currents across the plasma membrane were measured using whole cell patchclamp methods. These cells had a low conductance of 0.5 nS and resting potential of -50 mV. Depolarization activated a K+ current that was blocked by Ba2+. Steady-state current in absence of K+ was due to Cl- because of the magnitude of the reversal potential and the effects of Cl- removal. Stimulation of secretion by gastrin, cholecystokinin octapeptide (CCK-8), and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate activated the Cl- conductance with a time course similar to that of histamine release. Therefore the ECL cell maintains a high resting potential, largely due to K+ currents, and stimulation of secretion activates a Cl- current, perhaps deriving from the membrane of the secretory granule that fuses with the plasma membrane. The depolarization that ensues may activate the K+ current to maintain the membrane potential during exocytosis.

Animals↗
PubMed1995

Adjustments of public pension schemes in twelve industrialized countries: possible answers to population ageing.

"This article analyses the impact of population dynamics on future public pension expenditure in twelve industrialized countries. Whereas previous studies have mainly emphasized ageing effects, this study looks into the consequences of changing marital status structures as well. Old age pensions, disability, and survivor's pensions are investigated. Various sets of demographic and pension scenarios are formulated for the projections, dealing with changes in demographic, labour force and pension system variables in the future. The analyses show that there can be no adequate demographic response to rising pension costs caused by population ageing at the horizon 2030. Neither an increase in fertility nor an inflow of migrants can rejuvenate national populations, unless fertility and/or migration reach unrealistically high levels. Instead, substantial reductions of the public pension burden have to be sought in socioeconomic measures." (SUMMARY IN FRE)

Demography↗
PubMed1994

Cloning and expression of the rabbit gastric CCK-A receptor.

Cholecystokinin stimulates pancreatic zymogen secretion by binding with high affinity to a receptor on the pancreatic acinar cell. This receptor has been cloned and shown to be a CCK-A subtype. CCK also stimulates pepsinogen secretion from the gastric chief cell with high affinity. Using polymerase chain reaction with primers from the known sequence of the rat pancreatic CCK-A receptor cDNA, we prepared a 600 bp product from rat and rabbit stomach cDNA. From Southern analysis these represented a fragment of a gastric CCK-A receptor. PCR was then used to amplify a rabbit lambda ZAP II gastric epithelial cDNA library with the same primers, and the product was identified by sequencing as representing a CCK-A receptor fragment. When this PCR product was used to screen the library, ten positive clones were identified in a screening of 4.10(5) plaques, and several of these were sequenced. All had essentially the same sequence contained within 2 of these clones consisted of 427 amino acids and was 92% homologous (87% identity) to the known rat pancreatic CCK-A sequence but only 43% homologous to the gastric CCK-B sequence. The cDNA was subcloned into a pcDNA1 expression vector and transiently expressed in the human embryonic kidney cell line, HK 293. The responses of intracellular Ca2+ in these transfected cells to CCK and gastrin were monitored using video imaging. On the average 40% of the cells responded to CCK-8 by a transient elevation of [Ca2+]i followed by a steady state plateau. CCK was a high and gastrin a low affinity ligand for this signal, corresponding to the actions of these ligands on pepsinogen secretion from chief cells and somatostatin release from D cells. Hence from sequence and second messenger responses, the clone represents the CCK-A receptor presumably responsible for pepsinogen secretion by gastric chief cells and somatostatin release from gastric D cells.

Amino Acid Sequence↗
PubMed1994

The somatostatin receptor subtype on rat enterochromaffinlike cells.

BACKGROUND/AIMS: Gastric enterochromaffinlike (ECL) cells play an important role in peripheral regulation of acid secretion. This study investigated the somatostatin receptor subtype on ECL cells. METHODS: ECL cells were isolated from rat fundic mucosa to a purity of 90%-95% by combining enzymatic digestion, elutriation, density gradient centrifugation, and culture. RESULTS: Polymerase chain reaction performed with templates from an ECL cell complementary DNA library and primers specific to each of the five known somatostatin receptor subtypes showed that the somatostatin receptor type 2 was significantly enriched in ECL complementary DNA. Single cell videoimaging of highly purified ECL cells in culture showed that only the somatostatin receptor type 2 selective agonist, DC 32-87, inhibited the gastrin-induced calcium signal at 10(-11) mol/L. The type 3 and type 4 selective agonists, DC 25-12 and DC 32-92, and also somatostatin 14 required 100-1000 times higher concentrations (10(-8) mol/L). The somatostatin receptor type 2 analogue also inhibited gastrin-stimulated histamine release with a 50% inhibitory concentration (IC50) value of 2 x 10(-12) mol/L, whereas somatostatin 14 and the type 3 and 4 analogues showed IC50 values of 1 to 5 x 10(-9) mol/L. CONCLUSIONS: The predominant somatostatin receptors on rat gastric ECL cells are of the somatostatin receptor 2 subtype; they inhibit histamine secretion by interfering with the gastrin-induced calcium signal.

Amino Acid Sequence↗
PubMed1994

Continuing development of acid pump inhibitors: site of action of pantoprazole.

Both receptor antagonists and acid pump inhibitors are clinically useful suppressants of acid secretion. The latter class of drugs, the substituted benzimidazoles, inhibit acid secretion more effectively and, therefore, provide superior symptom relief and healing in all acid-related diseases. The H2-receptor antagonists competitively block the action of histamine on the H2-receptors of parietal cells. This histamine is released from enterochromaffin-like cells (ECL cells) due to gastrin, acetylcholine or epinephrine stimulation. In addition, parietal cells have M3-receptors which can function independently of H2-receptors. Hence, there is no single common pathway for parietal cell stimulation. Stimulation of acid secretion by parietal cells requires activation of the acid pump, the gastric H+,K(+)-ATPase. The target site for the benzimidazoles is the activated gastric H+,K(+)-ATPase, and, in particular, the cysteines of the pump that are exposed to the acid space of the secretory canaliculus of the parietal cells. Pantoprazole in its protonated form selectively reacts with cysteines present in both the fifth and sixth membrane segments of the ATPase, explaining its mechanism of inhibiting proton transport by this enzyme.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

Gastrin effects on isolated rat enterochromaffin-like cells in primary culture.

The hormone gastrin stimulates acid secretion by releasing histamine from gastric enterochromaffin-like (ECL) cells and induces ECL cell proliferation in vivo. This study uses a > 90% pure ECL cell preparation in culture to compare gastrin effects on histamine release, histidine decarboxylase (HDC) activity, and DNA synthesis. Gastrin and the cholecystokinin octapeptide (CCK-8, nonsulfated) induced histamine release from ECL cells (24-96 h of primary culture) within 5 min of incubation [concentration eliciting 50% of maximal response (EC50), 4 and 2 x 10(-11) M, respectively]. The CCK-B antagonist L-365,260 inhibited this effect [concentration inhibiting 50% of maximal response (IC50), 2 x 10(-8) M], whereas the CCK-A antagonist L-364,718 (10(-8) M) and the tyrosine kinase inhibitor genistein (10(-4) M) had no effect. Histamine release was associated with a biphasic elevation of intracellular Ca2+. Gastrin stimulated HDC activity two- to threefold after 60 min of incubation (EC50, 10(-10) M). Gastrin also increased DNA synthesis in ECL cells, with an EC50 of 1.7 x 10(-12) M as measured by the incorporation of 5-bromo-2'-deoxyuridine (BrdU). Positive nuclear immunostaining increased two- to threefold in up to 20% of ECL cells after 48-96 h of incubation. This effect was inhibited by L-365,260 (IC50, 5 x 10(-9) M) and by genistein (10(-4) M) but was not altered by L-364,718 (10(-8) M). The antisecretory drugs omeprazole, lansoprazole, and pantoprazole did not affect BrdU incorporation in isolated ECL cells. In conclusion, acute and chronic gastrin effects on the ECL cell are mediated via CCK-B receptors but differ in apparent receptor affinity and signal transduction pathways.

Animals↗
PubMed1994

Patterns of marriage and cohabitation in Europe, with emphasis on Sweden.

"This article attempts to describe the reasons for the emergence and the rapid increase of cohabitation [in Sweden] and can be used as the basis for assumptions about the future of cohabitation in other European countries. In addition, the article analyzes some interesting differences between married and cohabiting couples."

Developed Countries↗
PubMed1994

[Future changes in the age structure and the problem of pensions in the Austrian case].

Projections of rapid demographic aging in Austria are reviewed up to the year 2050. "After the turn of the century the proportion of the population above age 60 will gradually increase from 20% to at least 30 if not as much as 40 or 50% by 2050. During the same period the population above age 80 will be multiplied by four." It is argued that drastic pension reform is needed to guarantee future pension payments and avoid a large increase in the pension contribution rate. (SUMMARY IN ENG AND FRE)

Adult↗
PubMed1993

Antibody epitope mapping of the gastric H+/K(+)-ATPase.

Several antibodies against the gastric H+/K(+)-ATPase were analysed for the topological and sequence location of their epitopes. Topological mapping was done by comparing indirect immunofluorescent staining in intact and permeabilised rat parietal cells. Epitope definition was by Western analysis of intact and of trypsin or V8-proteinase-fragmented hog gastric ATPase combined with N-terminal sequencing of the fragments; by Western analysis of fragments of rabbit alpha subunit expressed in Escherichia coli; by analysis of rabbit alpha and beta subunits expressed in baculovirus-transfected SF 9 cells and by ELISA assay of synthetic octamers of one region of the hog alpha subunit. It was confirmed that the monoclonal antibody, mAb 95-111, recognised a cytoplasmic region between M4 and M5, close to the ATP-binding domain. The major epitope for monoclonal antibody mAb 12-18 was also in this region, but a second epitope was confirmed to be present in the M7/M8 region. The monoclonal antibody, mAb 146-14, was shown to recognise an extracytoplasmic epitope dependent on intact disulfide bonds, present in the rat and the rabbit, but absent in the hog beta subunit, due to non-conservative amino-acid substitutions. This antibody also recognised an epitope present in the alpha subunit of the H+/K(+)-ATPase at the M7 extracytoplasmic interface, perhaps indicating structural association of these two regions. The polyclonal antibody, pAb39, raised against the C-terminal portion of the enzyme, reacted only with the cytoplasmic surface of the H+/K(+)-ATPase, showing that the alpha subunit of the enzyme has an even number of membrane spanning segments.

Amino Acid Sequence↗
PubMed1993

Histamine secretion from rat enterochromaffinlike cells.

BACKGROUND: In vivo studies have suggested an important role for gastric enterochromaffinlike (ECL) cells in mediating acid secretion. Direct evidence for this function is lacking and requires a preparation of highly purified ECL cells. This work investigates the possible role and mechanism of histamine release from the ECL cell in the peripheral regulation of acid secretion, using purified ECL cells from rat fundic mucosa. METHODS: A combination of elutriation and density-gradient centrifugation was used to purify rat fundic ECL cells. Enrichment was determined by the presence of acidic vacuoles containing a V type adenosine triphosphatase, electron microscopy, immunostaining, and histamine content and release. RESULTS: ECL cells were enriched at least 65-fold with respect to the fundic epithelium. Gastrin (EC50 0.2 nmol/L) and cholecystokinin octapeptide (nonsulfated, EC50 0.04 nmol/L) stimulated histamine release in a time- and dose-dependent manner, suggesting a CCK-B receptor subtype, confirmed by the inhibition of gastrin/CCK stimulation with the CCK-B antagonist L365,260. Somatostatin also inhibited gastrin-mediated histamine release. Single cell imaging showed that gastrin elevated intracellular cytosolic calcium concentration biphasically. Carbachol and the C kinase activator 120-tetradecanoylphorbol-13-acetate also stimulated histamine release. Epinephrine (blocked by propranolol), forskolin, and dibutyryl-5'-cyclic adenosine monophosphate were also effective, implicating a beta-adrenergic pathway. The H3 agonist R-alpha-methyl-histamine inhibited, whereas the H3-antagonist thioperamide potentiated gastrin/CCK stimulated histamine release. CONCLUSIONS: These in vitro results support a central role for the ECL cell in the peripheral regulation of gastric acid secretion.

Animals↗
PubMed1993

The continuing development of gastric acid pump inhibitors.

The synthesis and action of H2-receptor antagonists changed the understanding of gastric acid secretion as well as changing medical therapy for peptic ulcer disease. It is now known that peripheral regulation of gastric acid secretion depends largely, but not entirely, on histamine release from the enterochromaffin-like cell. There is, therefore, no final common pathway for stimulation of the parietal cell. In contrast, all stimuli converge to activate the acid pump, the H+,K(+)-ATPase. Inhibition of this pump by clinically useful drugs was achieved by developing derivatives of timoprazole, pyridyl-2-methylsulfinyl benzimidazole. Two of these derivatives, omeprazole and lansoprazole, have shown superiority in acid control and therefore in therapy for peptic ulcer disease compared to the available H2-receptor antagonists.

Anti-Ulcer Agents↗