Inhibition of RNA synthesis by bradykinin involves both the B1 and B2 receptor subtypes.
The efficacy of angiotensin converting enzyme inhibitors in the treatment of heart disease is due in part to the accumulation of bradykinin (BK). Since BK can exert its effect by influencing cell proliferation, we chose to study the effect of BK on the growth of A10 vascular smooth muscle cells. Ligand binding studies to determine which BK receptor subtypes are present on A10 cells showed that both B1 and B2 receptors were present in approximately equal numbers. Examination of RNA synthesis demonstrated that BK inhibits uridine incorporation in a dose-dependent manner. This decrease in RNA synthesis was blocked by both B1 and B2 receptor antagonists, as well as by addition of indomethacin, a cyclooxygenase inhibitor. The latter result suggested that prostaglandins mediate the biological actions of BK. Consequently, we examined the direct effect of two prostaglandins, PGE2 and PGI2 (prostacyclin), on A10 cells. PGE2 caused a decrease in RNA synthesis, thus mimicking the effect of BK, while PGI2 did not. Therefore, the inhibition of RNA synthesis in A10 vascular smooth muscle cells by BK requires both B1 and B2 receptor subtypes and this action of BK is apparently mediated by de novo synthesis of prostaglandins.
Yau
L
L
Division of Cardiovascular Sciences, Department of Physiology, University of Manitoba, Winnipeg, Canada.
Pinsk
M
M
Zahradka
P
P
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D008024:Ligands; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000145:classification / Q000378:metabolism*
D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D008024:Ligands; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D001920:Bradykinin; D007213:Indomethacin