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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Iijima, T. Shibata, S. Ono, K. |
| Description | Author Affiliation: Shibata S ( Department of Pharmacology, Akita University School of Medicine, Akita 010-8543, Japan.) |
| Abstract | 1 The hyperpolarization-activated cation current (If) was recorded in single pacemaker cells of the porcine sino-atrial node, and the effects of genistein, an isoflavone inhibitor of tyrosine-specific protein kinases was investigated by the whole-cell patch clamp technique. 2 Genistein (20-500 microM) decreased If in a dose-dependent manner with an IC50 value of 62.3 microM and a maximum inhibition of 45.3%. 3 The effect on If appeared without altering the half-activation potential (control, -88.3+/-2.8 mV; genistein, -87.0+/-1.8 mV) and the slope factor (control, 8.0+/-0.3 mV; genistein, 8.6+/-0.7 mV) of the steady-state activation curve. No significant voltage-dependency was detected in the fully-activated current-voltage relation measured by the double-pulse protocols. 4 The inactive form of genistein analogue, daidzein (500 microM) or genistin (200 microM), were without effect. If was not affected by another tyrosine kinase inhibitor, tryphostin-47 (100 microM), but tyrphostin-25 (100-200 microM) suppressed If in an irreversible manner. 5 Neither bath nor intracellular application of the tyrosine phosphatase inhibitor, orthovanadate, affected If, and subsequent application of genistein inhibited If significantly. 6 These data indicate that the inhibition of If by genistein is not mediated through tyrosine kinase inhibition but through nonselective block of the If channels. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 6 |
| Volume Number | 128 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-11-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Genistein Pharmacology Ion Channels Drug Effects Membrane Potentials Sinoatrial Node Animals Dose-Response Relationship, Drug Electric Stimulation Electrophysiology Enzyme Inhibitors Physiology Isoflavones Kinetics Patch-Clamp Techniques Protein Tyrosine Phosphatases Antagonists & Inhibitors Protein-Tyrosine Kinases Cytology Swine Tyrphostins Vanadates Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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