Interaction of ovokinin(2-7) with vascular bradykinin 2 receptors.
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.
Scruggs
Phouangmala
P
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, P.O. Box 70577, Johnson City 37614, USA.
Filipeanu
Catalin M
CM
Yang
Jun
J
Chang
Jaw Kang
JK
Dun
Nae J
NJ
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000378:metabolism; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004527:Egg Proteins / Q000008:administration & dosage / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000378:metabolism / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014520:Urethane / Q000008:administration & dosage
D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D004527:Egg Proteins; D004963:Estrenes; D010446:Peptide Fragments; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; C096585:ovokinin; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D014520:Urethane; D010738:Type C Phospholipases; D001920:Bradykinin; D002118:Calcium