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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Altomare, Claudia Ferroni, Arnaldo Baruscotti, Mirko Bescond, Jocelyn Tognati, Agnese |
| Description | Author Affiliation: Altomare C ( Department of Biomolecular Sciences and Biotechnology, Laboratory of Molecular Physiology and Neurobiology, University of Milan, via Celoria 26, 20133 Milano, Italy.) |
| Abstract | Genistein is a tyrosine kinase inhibitor which interferes with the activity of several ionic channels either by altering modulatory phosphorylating processes or by direct binding. In whole-cell conditions, genistein induces a partial inhibition of the pacemaker (I(f)) current recorded in cardiac sinoatrial and ventricular myocytes. We investigated the mechanism of action of genistein (50 microM) on the I(f) current in whole-cell, cell-attached, and inside-out configurations, and the measured fractional inhibitions were similar: 26.6, 27.2, and 33.6%, respectively. When ATP was removed from the whole-cell pipette solution no differences were revealed in the effect of the drug when compared to metabolically active cells. Genistein fully maintained its blocking ability even when herbimycin, a tyrosine kinase inhibitor, was added to the whole-cell ATP-free pipette solution. Genistein-induced block was independent of the gating state of the channel and did not display voltage or current dependence; this independence distinguishes genistein from all other f-channel blockers. When inside-out experiments were performed to test for a direct interaction with the channel, genistein, superfused on the intracellular side of the membrane, decreased the maximal I(f) conductance, and slightly shifted the current-activation curve to the left. Furthermore, the effect of genistein was independent of cAMP modulation. We conclude that, in addition to its tyrosine kinase-inhibitory properties, genistein also blocks I(f) by directly interacting with the channel, and thus cannot be considered a valuable pharmacological tool to investigate phosphorylation-dependent modulatory pathways of the I(f) current and of cardiac rhythm. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 1 |
| Volume Number | 147 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2006-01-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Genistein Pharmacology Myocytes, Cardiac Drug Effects Pacemaker, Artificial Protein-Tyrosine Kinases Antagonists & Inhibitors Sinoatrial Node Animals Cells, Cultured Rabbits Cytology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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