Multiple Bradykinin Receptors: Results of Studies Using a Novel Class of Receptor Antagonists

  • Larry R. Steranka
  • Ronald M. Burch
  • Raymond J. Vavrek
  • John M. Stewart
  • Salvatore J. Enna
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 236)


Bradykinin is a nonapeptide that is generated in plasma and tissues in response to injury and infection. Once released, bradykinin exhibits physiological effects suggesting it is a mediator of the pain and inflame-mation associated with a variety of pathological conditions. Physiological effects include the stimulation and sensitization of nociceptive afferent neurons, vasodilation, increased vascular permeability and enhanced fluid secretion from epithelia. These actions are mediated by specific membrane receptors for bradykinin that exist in many tissues, including the nervous system, smooth muscle, epithelia and fibroblasts. Recently, a series of bradykinin analogues was described (Vavrek and Stewart, 1985) which includes specific, competitive antagonists of bradykinin-induced contraction of guinea pig ileum and rat uterus in vitro and of bradykinin-induced hypotension in vivo. These compounds hold great promise as novel analgesic/ anti-inflammatory agents and permit, for the first time, assessment of the physiological and pathophysiological roles of bradykinin. In the present report we describe results of studies of the effects of the antagonists on bradykinin receptor binding, receptor-coupled transduction systems, isolated smooth muscle, and in vivo animal models of pain and hyperalgesia. The results suggest that pharmacologically distinct types of bradykinin receptors may exist in different tissues.


Arachidonic Acid Release Tissue Kallikrein Bradykinin Receptor High Molecular Weight Kininogen Bradykinin Antagonist 
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Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Larry R. Steranka
    • 1
  • Ronald M. Burch
    • 1
  • Raymond J. Vavrek
    • 2
  • John M. Stewart
    • 2
  • Salvatore J. Enna
    • 1
  1. 1.6200 Freeport CentreNova Pharmaceutical CorporationBaltimoreUSA
  2. 2.Department of BiochemistryUniversity of Colorado School of MedicineDenverUSA

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