Detection of bradykinin B1 receptors in rat aortic smooth muscle cells.
The tritiated bradykinin B1 receptor agonist [3H]des-Arg(10)-kallidin bound to a single class of high-affinity binding sites (K(d) = 0.5 +/- 0.16 nM; B(max) = 15,000 +/- 8,000 sites/cell) on cultured rat aortic smooth muscle cells. [3H]Des-Arg(10)-kallidin association and dissociation kinetics were monoexponential, making it possible to determine the association and dissociation rate constants (k(+1) = 1.5 10(5) M(-1) sec(-1); k(-1) = 4.2 10(-5) sec(-1)). [3H]Des-Arg(10)-kallidin binding was inhibited by specific ligands of bradykinin B1 and B2 receptors with a rank order of potency consistent with that known for bradykinin B1 receptors in other species (des-Arg(9)-[Leu(8)]bradykinin = des-Arg(10)-kallidin = des-Arg(9)-bradykinin = des-Arg(10)-[Leu(9)]kallidin > des-Arg(10)-HOE-140 >> bradykinin >> HOE-140). Bradykinin B1 receptor mRNA was also detected in these cells. Des-Arg(10)-kallidin increased cytosolic free Ca2+ levels, phosphoinositide turnover, and arachidonic acid release at nanomolar concentrations (respective EC(50) values: 16 +/- 2, 4 +/- 2.7, 6 +/- 2 nM). These functional effects of des-Arg(10)-kallidin could be blocked by the bradykinin B1 receptor antagonist des-Arg(9)-[Leu(8)]bradykinin, but were not sensitive to bradykinin B2 receptor antagonists. These results therefore show that rat aortic smooth muscle cells in culture express functional bradykinin B1 receptors.
Schaeffer
P
P
Cardiovascular/Thrombosis Research Department, Sanofi-Synthelabo Recherche, 195 Route d'Espagne, F-31036, Toulouse, France.
Laplace
M C
MC
Savi
P
P
Prabonnaud
V
V
Salel
V
V
Herbert
J M
JM
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D007609:Kallidin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin / Q000032:analysis* / Q000235:genetics; D014316:Tritium
D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin; D014316:Tritium; D007609:Kallidin; C052787:kallidin, des-Arg(10)-