| Amiloride and analogues inhibit Na(+)-H+ exchange and cell proliferation in AR42J pancreatic cell line. | |
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MedLine Citation:
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PMID: 2173418 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To study the relation between activation of the Na(+)-H+ antiporter and gastrointestinal cell proliferation, we characterized this antiporter in a pancreatic cell line (AR42J) and studied the effects of mitogenic and nonmitogenic agents as well as those of Na(+)-H+ exchange blocking agents on DNA synthesis. Characteristics of amiloride-sensitive Na+ uptake were those of the Na(+)-H+ exchanger: 1) Na+ uptake was increased by intracellular acidification and depended on external [Na+] and pH; 2) concentrations for half-maximal inhibition (IC50) of Na+ uptake (3 mM [Na+] in medium) were 40 nM 5-(N,N-hexamethylene)amiloride (HA) less than 0.1 microM 5-(N-ethyl-N-isopropyl)amiloride (EIPA) less than 1 microM 5-(N,N-dimethyl)-amiloride (DMA) less than 40 microM amiloride; 3) IC50 for amiloride and analogues to inhibit Na+ uptake depended on [Na+] in medium (in 25 mM Na+ medium, the IC50 values were higher than in 3 mM and were 1 microM EIPA less than 10 microM DMA less than 0.3 mM amiloride). Growth factors for AR42J cells (dialyzed fetal calf serum and epidermal growth factor) activated Na+ uptake in a dose-dependent manner. Bombesin, which is nonmitogenic for AR42J cells, also increased Na+ uptake, indicating that activation of the antiporter is not sufficient to initiate cell proliferation in the AR42J cell line. The effects of Na(+)-H+ exchange blocking agents were tested on serum-stimulated cell proliferation. Decreasing external Na+ dramatically decreased AR42J cell proliferation. Amiloride and analogues inhibited [3H]thymidine incorporation in the same range of concentrations as that with which they inhibited Na(+)-H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS) |
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Authors:
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M Delvaux; M J Bastié; J Chentoufi; E J Cragoe; N Vaysse; A Ribet |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The American journal of physiology Volume: 259 ISSN: 0002-9513 ISO Abbreviation: Am. J. Physiol. Publication Date: 1990 Nov |
Date Detail:
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Created Date: 1990-12-11 Completed Date: 1990-12-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370511 Medline TA: Am J Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: G842-9 Citation Subset: IM |
Affiliation:
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Institut National de la Santé et de la Recherche Médicale, U151, CHU de Rangueil, Toulouse, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amiloride
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analogs & derivatives*,
pharmacology* Animals Carrier Proteins / antagonists & inhibitors* Cell Division / drug effects* Cell Line DNA Replication / drug effects Epidermal Growth Factor / pharmacology Kinetics Pancreas Sodium / metabolism* Sodium-Hydrogen Antiporter Thymidine / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/Sodium-Hydrogen Antiporter; 2609-46-3/Amiloride; 50-89-5/Thymidine; 62229-50-9/Epidermal Growth Factor; 7440-23-5/Sodium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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