Interaction of ovokinin(2-7) with vascular bradykinin 2 receptors

Regul Pept. 2004 Aug 15;120(1-3):85-91. doi: 10.1016/j.regpep.2004.02.019.

Abstract

Intravenous administration of ovokinin(2-7), a cleavage peptide derived from ovalbumin, dose-dependently (0.1-5 mg/kg) lowered the mean arterial pressure (MAP) that was not accompanied by a significant change in the heart rate (HR) of urethane-anesthetized rats. The hypotensive effects of ovokinin(2-7) were five orders of magnitude lower compared to that of bradykinin and were largely prevented by pretreatment with the bradykinin B2 receptor antagonist HOE140 (81.6 +/- 18.4%) and moderately affected by the B1 receptor antagonist [des-Arg10]-HOE140 (26.3 +/- 15.5%). Intracellular Ca2+ levels, as measured by Fur 2-AM, were significantly elevated in cultured aorta smooth muscle cells by ovokinin(2-7). The increases were abolished by HOE140 and unaffected by [des-Arg10]-HOE140. The elevation of intracellular Ca2+ by ovokinin(2-7) was dependent on Ca2+ entry from extracellular space as it was reduced in a Ca2+ -free solution. Pretreatment of the cells with the phospholipase C inhibitor U73122 (2 microM) eliminated the Ca2+ increase by the peptide. PA phosphohydrolase and phospholipase A2 inhibitors significantly reduced the responses as well. Our results show that ovokinin(2-7) modulates cardiovascular activity by interacting with B2 bradykinin receptors.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta / drug effects
  • Blood Pressure / drug effects
  • Bradykinin / analogs & derivatives*
  • Bradykinin / metabolism
  • Bradykinin B1 Receptor Antagonists
  • Bradykinin B2 Receptor Antagonists
  • Calcium / metabolism
  • Cells, Cultured
  • Egg Proteins / administration & dosage
  • Egg Proteins / metabolism*
  • Estrenes / pharmacology
  • Heart Rate / drug effects
  • Hypotension / metabolism
  • Hypotension / pathology
  • Male
  • Muscle, Smooth, Vascular / drug effects*
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / metabolism*
  • Phosphodiesterase Inhibitors / pharmacology
  • Pyrrolidinones / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Bradykinin B1 / metabolism*
  • Receptor, Bradykinin B2 / metabolism*
  • Type C Phospholipases / antagonists & inhibitors
  • Urethane / administration & dosage

Substances

  • Bradykinin B1 Receptor Antagonists
  • Bradykinin B2 Receptor Antagonists
  • Egg Proteins
  • Estrenes
  • Peptide Fragments
  • Phosphodiesterase Inhibitors
  • Pyrrolidinones
  • Receptor, Bradykinin B1
  • Receptor, Bradykinin B2
  • ovokinin
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Urethane
  • Type C Phospholipases
  • Bradykinin
  • Calcium