Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT
1) receptors in rabbit aorta and human recombinant AT
1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'
2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [
125I]AII binding to rabbit aortic membranes (AT, receptors) and [
125I][Sar
1, Ile
8]AII binding to human recombinant AT
1 receptors in a concentration-dependent manner with IC
50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [
125I)AII binding to bovine cerebellum membranes (ÀT
2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT
1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT
1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [
125I]AII binding assay and insurmountable AT
1 receptor antagonism in the functional study.
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