Tyrosine Kinase-Independent Extracellular Action of Genistein on the CFTR Cl- Channel in Guinea Pig Ventricular Myocytes and CFTR-Transfected Mouse Fibroblasts.
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- ZHOU Shi-Sheng
- Department of Cellular and Molecular Physiology, National Institute for Physiological Sciences Present address: Department of Physiology, The Fourth Military Medical University
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- HAZAMA Akihiro
- Department of Cellular and Molecular Physiology, National Institute for Physiological Sciences
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- OKADA Yasunobu
- Department of Cellular and Molecular Physiology, National Institute for Physiological Sciences
Bibliographic Information
- Other Title
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- Tyrosine Kinase-Independent Extracellul
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Abstract
The effects of genistein, a protein tyrosine kinase inhibitor, on the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel were studied in guinea pig ventricular myocytes and in NIH3T3 mouse fibroblasts stably transfected with CFTR cDNA by the whole-cell patch-clamp technique. Genistein did not activate whole-cell Cl- currents when applied to the intracellular (pipette) solution. In contrast, when applied to the extracellular solution, genistein alone promptly activated the Cl- current in a fully reversible manner. Also, extracellular genistein reversibly potentiated the forskolin-activated Cl- current. However, both basal and forskolin-activated Cl- currents were not affected by other protein tyrosine kinase inhibitors, including herbimycin A, lavendustin A, tyrphostin 21, tyrphostin 47, and tyrphostin 51. A nonspecific inhibitor of protein phosphatases, orthovanadate, had no effect on the genistein-induced activation of CFTR. Pretreatment with a protein kinase inhibitor, either H-89 or H-7, or with an adenylate cyclase inhibitor, SQ 22536, also had no effect on the genistein-induced response. Thus, it is concluded that genistein alone activates CFTR by a protein tyrosine kinase-independent and protein phosphatase-independent mechanism from the extracellular side, but not from the intracellular side.
Journal
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- The Japanese Journal of Physiology
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The Japanese Journal of Physiology 48 (5), 389-396, 1998
THE PHYSIOLOGICAL SOCIETY OF JAPAN
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Details 詳細情報について
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- CRID
- 1390001205042953600
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- NII Article ID
- 10008305487
- 30015529331
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- NII Book ID
- AA00691224
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- COI
- 1:CAS:528:DyaK1MXlvFWn
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- ISSN
- 18811396
- 0021521X
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- NDL BIB ID
- 4615132
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- PubMed
- 9852348
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed