Intracellular Calcium Transients Associated with Endothelium-Derived Relaxing Factor Release May Be Mediated by Inositol-1,4,5-Trisphosphate

  • Alex L. Loeb
  • Nicholas J. IzzoJr.
  • Randolph M. Johnson
  • James C. Garrison
  • Michael J. Peach
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


A large number of vasoactive agents induce relaxation by stimulating endothelial cells to release an endothelium-derived vascular relaxing factor (EDRF), an unstable and as yet unidentified compound. EDRF was first described by Furchgott and Zawadzki (1980) to relax preconstricted vascular smooth muscle. Since then, this compound has been demon strated to stimulate the soluble form of guanylate cyclase, but not adenylate cyclase, in vascular smooth muscle (Rapoport and Murad, 1983). Endothelium-derived vascular relaxing factor is not a product of cyclooxygenase, since indomethacin pretreatment does not affect EDRF-induced smooth-muscle relaxation (Furchgott and Zawadzki, 1980) or cyclic GMP accumulation (Peachet al., 1985). The compound has a short half-life (> 1 min; Griffithet al., 1984; Luckhoffet al., 1987) and its actions are blocked by a wide variety of substances without a common mechanism of action (Furchgott, 1983; Griffithet al., 1984; Peachet al., 1985).


Extracellular Calcium Bovine Aortic Endothelial Cell Inositol Trisphosphate Cytosolic Free Calcium Porcine Aortic Endothelial Cell 
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Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Alex L. Loeb
    • 1
  • Nicholas J. IzzoJr.
    • 2
  • Randolph M. Johnson
    • 3
  • James C. Garrison
    • 4
  • Michael J. Peach
    • 4
  1. 1.Department of AnesthesiaUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  2. 2.Cardiovascular DivisionBrigham and Women’s HospitalBostonUSA
  3. 3.Department of Biomolecular PharmacologyGenentech, Inc.South San FranciscoUSA
  4. 4.Department of PharmacologyUniversity of Virginia School of MedicineCharlottesvilleUSA

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