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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ko, Y. Seul, C. Vetter, H. Sachinidis, A. Düsing, R. |
| Description | Author Affiliation: Sachinidis A ( Medizinische Universitäts-Poliklinik, Bonn, Germany.) |
| Abstract | 1. Hoe 694 (3-methylsulphonyl-4-piperidinobenzoyl)guanidine methanesulphonate) was characterized as a new, potent, non-amiloride inhibitor of the Na+/H+ exchanger. In order to elucidate the role of the Na+/H+ exchanger isoform 1 (NHE-1) in the regulation of vascular smooth muscle cell growth, we investigated the effects of different amiloride analogues and of Hoe 694 on angiotensin II-induced cell growth. Since intracellular pH, the intracellular free Ca2+ concentration and the expression of the transcription factor c-fos seem to be involved in the regulation of cell growth, the effects of the amiloride analogues and Hoe 694 on the angiotensin II-induced changes in these three parameters were examined. 2. Measurement of cytosolic Ca2+ and pH in cell monolayers was performed using fura-2/AM and BCECF/AM, respectively. The effect of angiotensin II on cell growth was examined using (1) [3H]-thymidine incorporation, (2) the bromo-2-deoxyuridine (BrdU) immunfluorescence assay, (3) the colorimetric determination of cell mitochondrial dehydrogenase activity and (4) determination of cell number. Total RNA was extracted from cells by the guanidinium isothiocyanate/CsCl procedure. The expression of c-fos was quantitated by Northern blotting. 3. Various amiloride analogues inhibited the angiotensin II-induced stimulation of the Na+/H+ exchanger, the increase in cytosolic Ca2+ and cell growth but not the induction of c-fos mRNA. Hoe 694 (1-25 microM) dose-dependently inhibited the angiotensin II-induced stimulation of the Na+/H+ exchanger but had no significant effects on cytosolic Ca2+, c-fos mRNA levels or cell growth. 4. Our findings support the concept that activation of the Na+/H+ exchanger is not essential for angiotensin II-induced vascular smooth muscle cell growth. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 5 |
| Volume Number | 119 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1996-11-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Angiotensin II Pharmacology Guanidines Muscle, Smooth, Vascular Drug Effects Sodium-Hydrogen Antiporter Antagonists & Inhibitors Sulfones Animals Cell Division Cells, Cultured DNA Replication Drug Interactions Hydrogen-Ion Concentration Cytology Metabolism Rats, Inbred WKY Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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