Pharmacological properties of angiotensin II receptors in cultured rabbit gingival fibroblasts.
We demonstrated that angiotensin II (Ang II, 10-1000 nM) induced proliferation of cultured rabbit gingival fibroblasts in a concentration-dependent manner. The Ang II-induced proliferation was inhibited by CV-11974 (AT1 antagonist; 1 microM) and saralasin (AT1/AT2 antagonist; 1 microM), but not by PD123,319 (AT2 antagonist; 1 microM), suggesting that Ang II-induced proliferation was mediated via AT1 receptors present in and/or on gingival fibroblasts. The results of Western blot analysis indicated the presence of AT1 and AT2 receptors in/on the fibroblasts. In a subsequent radioligand binding assay, the binding of [3H]Ang II to the fibroblasts was specific and saturable with both high- and low-affinity sites. Competition binding experiments indicated that Ang II completely displaced [3H]Ang II binding, and CV-11974 and PD123,319 maximally displaced up to approximately 63% and 37% of the total binding, respectively. Ang II and CV-11974 completely displaced the [3H]DuP753 binding but PD123,319 did not, indicating a single population of binding site. These findings demonstrate that gingival fibroblasts contain both AT1 and AT2 receptor subtypes for Ang II, and support that Ang II stimulation of AT1 receptors results in proliferation of the fibroblasts.
Ohuchi
Nozomi
N
Department of Physiology and Anatomy, Nihon University College of Pharmacy, Narashinodai, Funabashi, Chiba 274-8555, Japan. Ohuchi@pha.nihon-u.ac.jp
Hayashi
Kazuhiko
K
Koike
Katsuo
K
Kizawa
Yasuo
Y
Kusama
Tadashi
T
Ohsawa
Masami
M
Taniguchi
Yumiko
Y
Iwamoto
Keishi
K
Sano
Masakazu
M
Murakami
Hajime
H
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D001713:Biphenyl Compounds; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005881:Gingiva / Q000166:cytology*; D007700:Kinetics; D019808:Losartan / Q000494:pharmacology; D011817:Rabbits; D011869:Radioligand Assay; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012504:Saralasin / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D014316:Tritium
D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D014316:Tritium; D000804:Angiotensin II; D012504:Saralasin; D019808:Losartan; C081643:candesartan