Human aortic smooth muscle cells containing angiotensin II type 1 receptors.
We characterized the angiotensin II (AII) receptor in human aortic smooth muscle cells (HASMCs). This receptor binds [125I]Sar1,Ile8-angiotensin II with a high affinity of 0.20 +/- 0.04 nM and a low capacity of 5.3 +/- 0.4 fmol/mg protein (230 +/- 17 sites/cell). Based on the Ki values, the ranking order of [125I]Sar1,Ile8-AII binding inhibition was as follows: Sar1,Ile8-AII > AII > Dup 753 > AII > AI >> PD 123319. The addition of AII to HASMCs induced a rapid, transient increase in intracellular free Ca2+ concentration followed by a lower, sustained phase. When extracellular Ca2+ was removed by adding 3 mM EGTA, this initial transient increase was not changed, but the sustained phase was abolished. These results revealed AII receptors in HASMCs to be of the type 1 receptor subtype, which induce Ca2+ mobilization mainly from intracellular Ca2+ stores.
Yazawa
H
H
Drug Serendipity Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan.
Iida-Kubota
E
E
Honda
K
K
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics / Q000494:pharmacology; D019808:Losartan; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011725:Pyridines / Q000493:pharmacokinetics / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013777:Tetrazoles / Q000493:pharmacokinetics / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; C009210:sarleucin; D019808:Losartan; D002118:Calcium