| Inhibition of parietal cell acid secretion is mediated by the classical epidermal growth factor receptor. | |
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MedLine Citation:
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PMID: 9201084 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) inhibit gastric acid secretion both in vivo and in vitro. Previous studies have indicated that EGF and TGF-alpha bind to the same EGF/TGF-alpha receptor. Nevertheless, we and others have previously demonstrated that inhibition of acid secretion by these growth factors requires concentrations of the peptides that are 10-fold higher than those necessary for induction of mitogenesis. Therefore, we have sought to investigate whether gastric parietal cells may possess a second EGF/TGF-alpha receptor class. Two systems were studied: First, [125I]TGF-alpha was cross-linked to the receptor in isolated rabbit parietal cell membranes, and labeled species were resolved on SDS-PAGE. Second, acid secretion was evaluated in pylorus-ligated waved-2 mutant mice, which carry a disabling point mutation in their classical EGF/TGF-alpha receptor. In isolated parietal cells, [125I]TGF-alpha was cross-linked into a single species of 170 kDa. Cross-linking was inhibited in the presence of unlabeled TGF-alpha with an IC50 of 80 nM. In the pylorus-ligated mice, control littermate mice demonstrated a dose-dependent inhibition of acid secretion by EGF with an IC50 of 20 micrograms/kg. In contrast, EGF had no inhibitory effect on acid secretion in waved-2 mice at concentrations up to 100 micrograms/kg. No alterations in parietal cell or gastrin cell numbers were observed. These results in both isolated rabbit parietal cells and waved-2 mice support the existence of only a single class of EGF/TGF-alpha receptors in parietal cells. Differences in growth factor affinity are likely due to the modification of the receptor or one of its coordinate regulators. |
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Authors:
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V Joshi; G S Ray; J R Goldenring |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Digestive diseases and sciences Volume: 42 ISSN: 0163-2116 ISO Abbreviation: Dig. Dis. Sci. Publication Date: 1997 Jun |
Date Detail:
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Created Date: 1997-07-16 Completed Date: 1997-07-16 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7902782 Medline TA: Dig Dis Sci Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1194-8 Citation Subset: AIM; IM |
Affiliation:
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Augusta Veterans Affairs Medical Center, Georgia, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Epidermal Growth Factor / pharmacology, physiology Gastric Acid / secretion Mice Mice, Mutant Strains Parietal Cells, Gastric / drug effects, secretion* Point Mutation Rabbits Receptor, Epidermal Growth Factor / classification, genetics, physiology* Transforming Growth Factor alpha / pharmacology, physiology |
| Grant Support | |
ID/Acronym/Agency:
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DK43405/DK/NIDDK NIH HHS; DK48370/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Transforming Growth Factor alpha; 62229-50-9/Epidermal Growth Factor; EC 2.7.10.1/Receptor, Epidermal Growth Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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