Peptide growth factors markedly decrease the ligand binding of angiotensin II type 2 receptor in rat cultured vascular smooth muscle cells.
Of two major isoforms of angiotensin II receptors, AT1 and AT2, biological roles of AT2 remain unclear. Using vascular smooth muscle cells, we investigated the regulation of expression of AT2 by growth factors in comparison with that of AT1. The cultured rat aorta smooth muscle cells had detectable AT2 binding sites, which were reduced significantly by treatment with platelet derived growth factor-BB. On the other hand, AT1 binding sites were increased under the same conditions. Other growth factors, such as epidermal growth factor and endothelin-1, also suppressed AT2 receptors to varying extents. A negative correlation between DNA synthesis promoted by these growth factors and the binding capacity of AT2 sites was observed. This study indicated that the expression of AT2 is downregulated in cultured vascular smooth muscle cells by growth factors in contrast to that of AT1, which was slightly upregulated.
Kambayashi
Y
Y
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Bardhan
S
S
Inagami
T
T
D000704:Analysis of Variance; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication; D016232:Endothelins / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007700:Kinetics; D008024:Ligands; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism
D016232:Endothelins; D008024:Ligands; D010982:Platelet-Derived Growth Factor; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D004815:Epidermal Growth Factor; D013936:Thymidine