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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Author(s)

Abstract

The effects of genistein, a protein tyrosine kinase inhibitor, on the cystic fibrosis transmembrane conductance regulator (CFTR) Cl<SUP>-</SUP> 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<SUP>-</SUP> currents when applied to the intracellular (pipette) solution. In contrast, when applied to the extracellular solution, genistein alone promptly activated the Cl<SUP>-</SUP> current in a fully reversible manner. Also, extracellular genistein reversibly potentiated the forskolin-activated Cl<SUP>-</SUP> current. However, both basal and forskolin-activated Cl<SUP>-</SUP> 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

  • The Japanese Journal of Physiology

    The Japanese Journal of Physiology 48(5), 389-396, 1998-10

    THE PHYSIOLOGICAL SOCIETY OF JAPAN

References:  30

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008305487
  • NII NACSIS-CAT ID (NCID)
    AA00691224
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    0021521X
  • NDL Article ID
    4615132
  • NDL Source Classification
    ZS8(科学技術--医学--解剖学・生理学・生化学)
  • NDL Call No.
    Z53-D40
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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