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Biomedical subjects

C Prinz

Publications and source records attributed to C Prinz.

At least 19 recordsLinked to original sources
PubMed2006

Lack of RUNX3 regulation in human gastric cancer.

It has been proposed that the transcription factor RUNX3 is the product of a gastric tumour suppressor gene. We examined RUNX3 expression in gastric biopsies from 105 patients with different histological presentations. Surprisingly, immunohistochemical staining detected RUNX3 protein expression only in infiltrating leukocytes but not in the gastric epithelium. Using laser capture microdissection and quantitative reverse transcription-polymerase chain reaction, we confirmed that the level of RUNX3 mRNA expression in the gastric epithelium was very low and was influenced neither by H. pylori infection nor by neoplastic transformation. Instead, RUNX3 was highly expressed in the gastric stroma and the level of expression correlated with the magnitude of H. pylori-induced gastric inflammation. The low level of RUNX3 expression in gastric epithelium and the absence of downregulation in gastric cancer do not support the hypothesis that RUNX3 functions as a gastric tumour suppressor gene.

Adenocarcinoma↗
PubMed2006

Argon plasma ablation of gastric inlet patches in the cervical esophagus may alleviate globus sensation: a pilot trial.

BACKGROUND AND STUDY AIMS: Globus sensation and/or sore throat have been associated with both gastroesophageal reflux disease and the presence of a gastric inlet patch. There have been no reports, however, on whether ablation of heterotopic mucosa in the cervical esophagus leads to improvement of chronic globus sensation. PATIENTS AND METHODS: Ten patients with a histologically proved gastric inlet patch who complained of chronic globus sensation and/or sore throat were included in this prospective pilot study. After a thorough assessment, including videofluoroscopy, laryngoscopy, manometry, and 24-hour two-channel pH monitoring, patients underwent argon plasma coagulation (APC) to ablate the heterotopic mucosa. A questionnaire with a visual analog scale ranging from 0 to 10 was used for assessment of globus sensation, sore throat, and other typical or atypical reflux symptoms. Follow-up examinations (including symptom assessment) were performed 4 weeks and 8 weeks after APC therapy. RESULTS: Ablation of the gastric inlet patch resulted in a significant reduction of median symptom scores for globus sensation (from 2.7 to 0) and sore throat (from 2.8 to 0) 8 weeks after therapy ( P < 0.05), but there was no improvement in other reflux-related symptoms. Acid reflux in the distal and proximal esophagus, determined by two-channel pH monitoring, did not change after therapy. CONCLUSIONS: Our preliminary data suggest that ablation of gastric inlet patches by APC can alleviate chronic globus sensation or sore throat. Acid reflux or its treatment is unlikely to influence these results. A randomized and blinded study is warranted.

Adult↗
PubMed2006

Hemodynamics after endoscopic submucosal injection of epinephrine in patients with nonvariceal upper gastrointestinal bleeding: a matter of concern.

We report about detailed hemodynamic changes and one major cardiac complication occurring after submucosal injection of epinephrine (1 : 10 000) for management of upper gastrointestinal bleeding in a series of four consecutive patients. Cardiac contractility and afterload, determined by the cardiac index and the systemic vascular resistence index (SVRI), were assessed by transpulmonary thermodilution using the Pulse Contour Cardiac Output monitoring system (PiCCO; Pulsion Medical Systems, Munich, Germany), and the mean arterial pressure and heart rate were recorded. We observed a distinct rise in both mean arterial pressure and heart rate, and this effect was pronounced in the three patients with esophageal lesions. The increase in the mean arterial pressure was caused by an elevation of the cardiac index in two patients, a rise in both cardiac index and SVRI in one patient, and a rise in the SVRI only in the fourth patient. One patient, who had received 30 ml epinephrine for treatment of a bleeding Mallory-Weiss tear, developed an acute myocardial infarction during the postprocedural follow-up period. In conclusion, submucosal injection of epinephrine may cause significant hemodynamic changes that can potentially lead to adverse cardiac events. Close cardiac monitoring during and after submucosal application of epinephrine therefore seems a prudent precaution. In the treatment of esophageal lesions, the total amount of epinephrine injected should be carefully titrated, so that the lowest possible volume that achieves adequate hemostasis is used.

Adult↗
PubMed2005

A prospective multicenter clinical and endoscopic follow-up study of patients with gastroesophageal reflux disease.

BACKGROUND: Despite its high prevalence, data on the course of gastroesophageal reflux disease (GERD) are still sparse. There is also an ongoing debate on the natural history of its various manifestations, i.e., non-erosive reflux disease (NERD) vs. erosive reflux disease (ERD) vs. Barrett's esophagus (BE). PATIENTS AND METHODS: This study was conducted within the framework of a prospective multicenter study on the course and prevalence of intestinal metaplasia at the gastroesophageal junction. 1014 dyspeptic patients were screened by the means of upper GI endoscopy. Clinical data were recorded by the use of a questionnaire. At least 15 months after the initial examination, all patients were invited for follow-up (FU) examination. Patients were analyzed separately with respect to their clinical and endoscopic findings. For the latter, only patients without any treatment with proton-pump-inhibitors (PPI) prior to initial and follow-up examinations were included. Patients were categorized as GERD positive if typical symptoms were present and/or proton pump inhibitors were used. RESULTS: Sufficient clinical and/or endoscopic data were available in 590 GERD patients with heartburn at least once a week. Follow-up data could be obtained in 320 patients (clinical FU: n = 304; endoscopic FU: n = 52) after a mean follow-up period of 35 months (18-48 months). 96 of 144 previously asymptomatic patients (67%) remained asymptomatic at follow-up, the rest (n = 48) were symptomatic. 143 of 304 previously symptomatic patients (47%) were symptom-free at follow-up, and only 161 patients (53%) remained symptomatic or had concomitant therapy with proton-pump-inhibitors (PPI). For follow-up endoscopy in patients off PPI (n = 52), ERD was no longer confirmed in 7/12 ERD patients (58%), whereas progress to ERD was found in 3/34 patients (9%) in the NERD group. BE was newly diagnosed in two NERD patients but could no longer be detected in 2 of 6 patients with an initial diagnosis of BE. CONCLUSIONS: With respect to its clinical as well as its endoscopic manifestations, gastroesophageal reflux disease does not appear to be very stable over time. However, in most cases this is due to regression rather than progression of the disease.

Endoscopes, Gastrointestinal↗
PubMed2004

[Intraoperative laparoscopic cholangiography -- when is it useful?].

Since the introduction of laparoscopic cholecystectomy (LC), a decrease in the practice of intraoperative cholangiography (IOC) has been reported. Are there actually reasons for carrying on IOC during LC? Depending on the management of common bile duct (CBD) stones treatment a different IOC regime is recommended. If the single-stage laparoscopic extraction of ductal calculi during LC is preferred, routine IOC is generally necessary to detect all CBD stones for desobstruction via ductus cysticus or choledochotomy. When therapeutic splitting is favoured, including two-stage management with endoscopic desobstruction and later LC, routine IOC can be foregone. However, selective practice of IOC can help to reduce the rates of unnecessary preoperative investigations from 40-60 % to 20 % when postoperative endoscopic desobstruction demonstrates similar success rates of about 95 %. Regarding the preventive character of laparoscopic IOC to CBD injuries, a routine investigation should be adopted by institutions with injury rates > 0.4 % and in the learning phase of young surgeons. For all other institutions a selective practice should be recommended when difficult intraoperative conditions render recognition of the anatomical situation more difficult or for identification of dissected non-bleeding ducts near the triangle of Calot.

Cholangiography↗
PubMed2004

Isolation and receptor profiling of ileal enterochromaffin cells.

AIM AND METHODS: Enterochromaffin (EC) cells, interspersed throughout the gastrointestinal mucosa, provide most of the serotonin of the body and control intestinal motility, secretion and absorption. We purified EC cells from the rat ileum by a combination of elutriation and density gradient centrifugation in order to characterize the function of this important cell type. RESULTS: Immunostaining showed that there were 84% serotonin-positive cells in the highly enriched EC fraction as compared with 12% in unfractionated cells, yielding a approximately sevenfold enrichment. Serotonin measurements in the cell suspensions indicated a seven to 14-fold enrichment. Presence of alpha- and beta-adrenoreceptor isoforms, muscarinic M3 and gama-aminobutyric acid (GABA)-A receptors was confirmed by RT-PCR and cytochemistry. Increased expression of VMAT-1 and GABA-A mRNA was also shown by quantitative TaqMan PCR using EC cell RNA. Serotonin release in isolated EC cells was stimulated by noradrenaline, and to a smaller extent, by carbachol, while GABA addition was without effect. CONCLUSION: Our data provide a basis for a new approach to characterize receptors on this unique cell type.

Animals↗
PubMed2004

Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonisation during Helicobacter pylori infection.

BACKGROUND AND AIMS: Recent studies linked cytokine gene polymorphisms to H pylori related gastric cancer development. The current study evaluated the role of cytokine gene polymorphisms for mucosal cytokine expression, the gastric inflammatory response, and bacterial colonisation during H pylori infection. PATIENTS AND METHODS: In 207 H pylori infected patients with chronic gastritis, polymorphisms at different loci of the interleukin (IL)-10, IL-1B, IL-1 receptor antagonist (IL-1RN), tumour necrosis factor (TNF)-A, and interferon (IFN)-G genes were genotyped by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) analysis, and allelic discriminating TaqMan PCR. Mucosal cytokine mRNA copy numbers were determined by real time quantitative PCR. Presence of bacterial virulence factors was investigated by cagA, vacAs1/2, and babA2 PCR. Biopsies were assessed with regard to the degrees of granulocytic/lymphocytic infiltration and the presence of intestinal metaplasia (IM) and atrophic gastritis (AG). RESULTS: Proinflammatory IL-1 polymorphisms (IL-1RN*2(+)/IL-1B-511T/-31C(+)) were associated with increased IL-1beta expression, more severe degrees of inflammation, and an increased prevalence of IM and AG. Carriers of the IL-10-1082G/-819C/-592C alleles (GCC haplotype) had higher mucosal IL-10 mRNA levels than ATA haplotype carriers and were associated with colonisation by more virulent cagA(+), vacAs1(+), and babA2(+) H pylori strains. The TNF-A-307(G/A) and IFN-G+874(A/T) polymorphisms did not influence mucosal cytokine expression or the inflammatory response to H pylori. CONCLUSIONS: Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and the long term development of precancerous lesions in H pylori infection. Host polymorphisms are associated with certain bacterial strain types, suggesting host specific colonisation or adaptation. These findings contribute to the understanding of the complex interplay between host and bacterial factors involved in the development of gastric pathology.

Adult↗
PubMed2003

LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1.

We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as gamma chain (gamma(c)) deficiency] in 9 out of 10 patients by retrovirus-mediated gamma(c) gene transfer into autologous CD34 bone marrow cells. However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with gammadelta+ or alphabeta+ T cell receptors) has occurred in the two youngest patients. Both patients' clones showed retrovirus vector integration in proximity to the LMO2 proto-oncogene promoter, leading to aberrant transcription and expression of LMO2. Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Specific identification of three low molecular weight membrane-associated antigens of Helicobacter pylori.

BACKGROUND: A large number of Helicobacter pylori proteins are antigenic, but antibodies to these proteins persist in spite of the eradication of the infection. METHODS AND RESULTS: The analysis of sera from H. pylori-infected and non-infected patients, before and 3 and 5 months after eradication, showed that the antibody response against unknown H. pylori antigens at 32, 30, 22 and 14 kDa in sodium dodecylsulphate polyacrylamide gel electrophoresis decreased by > or = 60% at 3 months and > or = 70% at 5 months after treatment. Two-dimensional gel electrophoresis and mass spectrometry allowed the identification of eight proteins at these positions: neuraminyl-lactose-binding haemagglutinin precursor, 3-oxoadipate CoA-transferase subunit A, elongation factor P, peptidoglycan-associated lipoprotein precursor, hypothetical protein HP0596, adhesin-thiol peroxidase, 50S ribosomal protein L7/L12 and subunit b' of the F(0) ATP synthase. Three of these eight, expressed as recombinant proteins (32 kDa neuraminyl-lactose-binding haemagglutinin precursor, 30 kDa peptidoglycan-associated lipoprotein precursor and 22 kDa hypothetical protein HP0596), reacted specifically with sera from infected patients, while the 14 kDa 50S ribosomal protein L7/L12 cross-reacted with one out of five sera from H. pylori-negative patients. The other recombinant proteins did not show significant immunoreactivity. CONCLUSIONS: Four low molecular weight antigens were identified by these methods, three of which were specific. Immunoreaction with these three proteins (neuraminyl-lactose-binding haemagglutinin precursor, peptidoglycan-associated lipoprotein precursor and hypothetical protein HP0596) could provide a serological assessment not only of H. pylori infection, but also of eradication.

Aged↗
PubMed2001

Key importance of the Helicobacter pylori adherence factor blood group antigen binding adhesin during chronic gastric inflammation.

Helicobacter pylori has been assigned as a class I carcinogen because of its relation to gastric adenocarcinoma. Chronic H. pylori infection may lead to severe gastritis, glandular atrophy (AT), and intestinal metaplasia (IM). Strains secreting the vacuolating toxin VacA and producing the cytotoxin-associated antigen CagA (type 1 strains), as well as the blood group antigen binding adhesin (BabA) targeting Lewis(b) antigens, have been associated previously with distal gastric adenocarcinoma (M. Gerhard et al., Proc. Natl. Acad. Sci. USA, 96: 12778-12783, 1999) and may therefore also be related to lesions preceding gastric cancer. Antral and corpus biopsies were collected from 451 patients; 151 were H. pylori positive, as determined by PCR. Gastric biopsies were histologically evaluated for activity of gastritis (G0-G3, granulocyte infiltration), chronicity of gastritis (L1-L3, lymphocyte infiltration), and the presence of IM and/or AT according to the Sydney classification. Simultaneously, the presence of bacterial genes encoding virulence and adherence factors (racAs1/s2, cagA, and babA2) was determined by PCR. The presence of cagA+ and vacAs1 (alone or combined) both correlated with activity and chronicity of gastritis (P < 0.05); however, the overall prevalence of these genes was 60 or 72%, respectively, and was thus relatively frequent. The babA2 gene, encoding the adhesin BabA, was detected in 38% of infected patients and was correlated with the activity of gastritis in antrum and corpus (P < 0.005). cagA+/vacAs1+ strains (suggesting the presence of type 1 strains) that were also babA2 positive were detected more frequently in patients with severe histological alterations (such as G3, IM, or AT) compared with subjects without these changes (P < 0.01). cagA+/vacAs1+ strains that were babA2 negative, however, lacked a significant correlation with severe histological changes, activity, or chronicity of gastritis in antrum and corpus. Adherence of H. pylori via BabA appears to be of importance for efficient delivery of VacA and CagA and may play a special role in the pathogenesis of severe histological changes.

Adhesins, Bacterial↗
PubMed2001

Gastrin induces expression and promoter activity of the vesicular monoamine transporter subtype 2.

Gastric enterochromaffin-like cells produce histamine in response to the antral hormone gastrin and accumulate the biogenic amine in secretory organelles via vesicular monoamine transporter subtype 2. The putative effects of gastrin on vesicular monoamine transporter subtype 2 expression and promoter activity are poorly understood. In the present study we used highly enriched rat enterochromaffin-like cells (purity, >90%) and rat pheochromocytoma cells stably transfected with a gastrin/cholecystokinin B receptor to investigate the expression and transcriptional regulation of vesicular monoamine transporter subtype 2. Stimulation of vesicular monoamine transporter subtype 2 mRNA and protein expression was observed in isolated enterochromaffin-like cells after 3- to 7-h incubation with gastrin (10(-7) M), forskolin (10(-5) M), or ionomycin (10(-5) M). Deletion analysis of the rat vesicular monoamine transporter subtype 2 promoter defined the minimal promoter sequence necessary for full basal activity as a -121 bp segment upstream of exon 1 containing two Sp1 sites (-97 to -88 bp and -68 to -59 bp) and a cAMP-responsive element (-44 to -35 bp). Gastrin (10(-7) M) stimulated extracellular signal related kinase1/2 phosphorylation, activated Sp1 and cAMP-responsive element-binding protein, and further induced activity of the complete rat vesicular monoamine transporter subtype 2 promoter (-800 bp) in gastrin/cholecystokinin B receptor cells. The -121-bp fragment was able to confer full gastrin responsiveness, and site-directed mutagenesis of the Sp1 and cAMP-responsive element motifs demonstrated their crucial importance for basal and inducible activities. Comparison of promoter activity of histidine decarboxylase, chromogranin A, or vesicular monoamine transporter subtype 2 in transfected cell lines revealed significant differences in basal and gastrin-stimulated activities. Our current study provides the first evidence that gastrin directly stimulates the expression and promoter activity of vesicular monoamine transporter subtype 2. Sp1 and cAMP-responsive element-binding protein recognition motifs located within 121 bp upstream of exon 1 appear to be indispensable for full basal and inducible promoter activities. Diverging effects of gastrin on histidine decarboxylase, chromogranin A, and vesicular monoamine transporter subtype 2 promoter may account for the coordinated synthesis and storage of histamine in this neuroendocrine cell type.

Animals↗
PubMed2000

Biophysical and lipofection studies of DOTAP analogs.

In order to investigate the relationship between lipid structure and liposome-mediated gene transfer, we have studied biophysical parameters and transfection properties of monocationic DOTAP analogs, systematically modified in their non-polar hydrocarbon chains. Stability, size and (by means of anisotropy profiles) membrane fluidity of liposomes and lipoplexes were determined, and lipofection efficiency was tested in a luciferase reporter gene assay. DOTAP analogs were used as single components or combined with a helper lipid, either DOPE or cholesterol. Stability of liposomes was a precondition for formation of temporarily stable lipoplexes. Addition of DOPE or cholesterol improved liposome and lipoplex stability. Transfection efficiencies of lipoplexes based on pure DOTAP analogs could be correlated with stability data and membrane fluidity at transfection temperature. Inclusion of DOPE led to rather uniform transfection and anisotropy profiles, corresponding to lipoplex stability. Cholesterol-containing lipoplexes were generally stable, showing high transfection efficiency at low relative fluidity. Our results demonstrate that the efficiency of gene transfer mediated by monocationic lipids is greatly influenced by lipoplex biophysics due to lipid composition. The measurement of fluorescence anisotropy is an appropriate method to characterize membrane fluidity within a defined system of liposomes or lipoplexes and may be helpful to elucidate structure-activity relationships.

Anisotropy↗
PubMed2000

IL-1beta-induced apoptosis in rat gastric enterochromaffin-like cells is mediated by iNOS, NF-kappaB, and Bax protein.

BACKGROUND & AIMS: Enterochromaffin-like (ECL) cells are histamine-containing endocrine cells in the gastric mucosa. Previous studies have shown that the proinflammatory cytokine interleukin (IL)-1beta present during chronic gastritis inhibits histamine synthesis in ECL cells and leads to sustained functional impairment. This study investigated the effects of IL-1beta on ECL cell apoptosis and the related signal-transduction mechanisms. METHODS: ECL cells were isolated by pronase digestion and a combination of elutriation, gradient centrifugation, and 48-hour culture (purity >/=90%). Apoptosis was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling reaction and cell death detection enzyme-linked immunosorbent assay. RESULTS: IL-1beta (100 pg/mL) increased the rate of programmed cell death 2-3 fold in ECL cells after 24 hours of incubation (total of 12%-14%). This effect was completely inhibited by the NF-kappaB inhibitor, proteasome inhibitor I, and the nitric oxide synthase inhibitor (iNOS) N(G)-monomethyl-L-arginine (10(-4) mol/L), but not by the caspase 3 inhibitor, Asp-Glu-Val-Asp-CHO. Western blot analysis, reverse-transcription polymerase chain reaction (PCR), and in situ PCR showed that IL-1beta induced gene expression (after 2-4 hours) and protein synthesis (6-18 hours) of the iNOS isoform in ECL cells. Bax protein expression was increased in response to IL-1beta. In contrast, bcl-2 gene expression was increased in response to basic fibroblast growth factor, which has been shown to counteract IL-1beta- induced apoptosis. CONCLUSIONS: These data suggest that IL-1beta induces programmed cell death in isolated rat ECL cells via activation of NF-kappaB, iNOS, and the Bax protein.

Animals↗
PubMed1999

Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin.

Infection with Helicobacter pylori is associated with different human gastric diseases. Biochemical studies, in vitro adherence assays, and in vivo animal models revealed that epithelial attachment of H. pylori can be mediated by the blood-group antigen-binding adhesin (BabA) targeting human Lewis(b) surface epitopes. Studies with transgenic mice expressing the Lewis(b) epitope have shown that such attachment can alter disease outcome. In the current study, the presence of the babA2 gene encoding the adhesin was investigated in clinical isolates from a German population by using PCR and reverse transcription-PCR. A positive genotype was correlated to allelic variations in the genes encoding VacA and CagA and also to the prevalence of duodenal ulcer, distal gastric adenocarcinoma, mucosa-associated lymphoid tissue lymphoma, and antral gastritis. The presence of babA2 was significantly associated with duodenal ulcer (P = 0.0002) and adenocarcinoma (P = 0.033). In contrast, type 1 strains (vacAs1- and cagA-positive) were associated with only duodenal ulcer (P = 0.004) but not adenocarcinoma (P = 0.235). Genotype presence of babA2, vacAs1, and cagA ("triple-positive" strains) showed a highly significant correlation to the prevalence of ulcer (P = 0.000002) and adenocarcinoma (P = 0.014) and discriminated significantly better between disease outcome than did the current type 1 classification. These results indicate that the babA2 gene is of high clinical relevance and would be a useful marker to identify patients who are at higher risk for specific H. pylori-related diseases.

Adhesins, Bacterial↗
PubMed1999

The mechanism of histamine secretion from gastric enterochromaffin-like cells.

Enterochromaffin-like (ECL) cells play a pivotal role in the peripheral regulation of gastric acid secretion as they respond to the functionally important gastrointestinal hormones gastrin and somatostatin and neural mediators such as pituitary adenylate cyclase-activating peptide and galanin. Gastrin is the key stimulus of histamine release from ECL cells in vivo and in vitro. Voltage-gated K(+) and Ca(2+) channels have been detected on isolated ECL cells. Exocytosis of histamine following gastrin stimulation and Ca(2+) entry across the plasma membrane is catalyzed by synaptobrevin and synaptosomal-associated protein of 25 kDa, both characterized as a soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein. Histamine release occurs from different cellular pools: preexisting vacuolar histamine immediately released by Ca(2+) entry or newly synthesized histamine following induction of histidine decarboxylase (HDC) by gastrin stimulation. Histamine is synthesized by cytoplasmic HDC and accumulated in secretory vesicles by proton-histamine countertransport via the vesicular monoamine transporter subtype 2 (VMAT-2). The promoter region of HDC contains Ca(2+)-, cAMP-, and protein kinase C-responsive elements. The gene promoter for VMAT-2, however, lacks TATA boxes but contains regulatory elements for the hormones glucagon and somatostatin. Histamine secretion from ECL cells is thereby under a complex regulation of hormonal signals and can be targeted at several steps during the process of exocytosis.

Enterochromaffin Cells↗
PubMed1998

Voltage-gated Ca2+ currents in rat gastric enterochromaffin-like cells.

Enterochromaffin-like (ECL) cells are histamine-containing endocrine cells in the gastric mucosa that maintain a negative membrane potential of about -50 mV, largely due to voltage-gated K+ currents [D. F. Loo, G. Sachs, and C. Prinz. Am. J. Physiol. 270 (Gastrointest Liver Physiol. 33): G739-G745, 1996]. The current study investigated the presence of voltage-gated Ca2+ channels in single ECL cells. ECL cells were isolated from rat fundic mucosa by elutriation, density gradient centrifugation, and primary culture to a purity > 90%. Voltage-gated Ca2+ currents were measured in single ECL cells using the whole cell configuration of the patch-clamp technique. Depolarization-activated currents were recorded in the presence of Na+ or K+ blocking solutions and addition of 20 mM extracellular Ca2+. ECL cells showed inward currents in response to voltage steps that were activated at a test potential of around -20 mV with maximal inward currents observed at +20 mV and 20 mM extracellular Ca2+. The inactivation rate of the current decreased with increasingly negative holding potentials and was totally abolished at a holding potential of -30 mV. Addition of extracellular 20 mM Ba2+ instead of 20 mM Ca2+ increased the depolarization-induced current and decreased the inactivation rate. The inward current was fully inhibited by the specific L-type Ca2+ channel inhibitor verapamil (0.2 mM) and was augmented by the L-type Ca2+ channel activator BAY K 8644 (0.07 mM). We conclude that depolarization activates high-voltage-activated Ca2+ channels in ECL cells. Activation characteristics, Ba2+ effects, and pharmacological results imply the presence of L-type Ca2+ channels, whereas inactivation kinetics suggest the presence of additional N-type channels in rat gastric ECL cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗