title: Inhibition of the angiotensin II Type 1 receptor by TCV-116: quantitation by in vitro autoradiography.
abstract: Inhibition of angiotensin (Ang) II type 1 (AT1) receptors in various target tissues of adult Sprague-Dawley rats was studied after single oral administration of TCV-116. The effects of TCV-116 on Ang II-receptor binding were assessed by quantitative in vitro autoradiography using 125I-[Sar1,Ile8]Ang II as a ligand. Four hours after the administration of TCV-116 (1 mg/kg), Ang II-receptor binding was markedly inhibited in the kidney (20% of control), adrenal cortex (27%), thoracic aorta (57%), heart (55%) and testis (76%) where AT1 receptors predominate. In the brain, orally administered TCV-116 produced a significant inhibition of binding both to the circumventricular organs (38%), which are devoid of the blood-brain barrier (BBB), and to the discrete regions within the BBB such as the paraventricular hypothalamic nucleus (48%), nucleus of the solitary tract (60%). Twenty-four hours after the administration, Ang II-receptor binding had partly recovered to approximately 50-85% of control levels. In contrast, throughout the experimental period, Ang II-receptor binding was little affected in sites where Ang II type 2 (AT2) receptors predominate such as the adrenal medulla and the nucleus of the inferior olive. These data indicate that orally administered TCV-116 specifically binds to AT1 receptors both in peripheral tissues and the central nervous system.
authors: Department of Pharmacology, Osaka Medical College, Takatsuki, Japan.
authors: K
authors: K
authors: Song
authors: H
authors: H
authors: Kanehara
authors: S
authors: S
authors: Takai
authors: N
authors: N
authors: Shiota
authors: T
authors: T
authors: Wada
authors: Y
authors: Y
authors: Inada
authors: M
authors: M
authors: Miyazaki
mesh_terms: D000284:Administration, Oral; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism / Q000494:pharmacology*; D001345:Autoradiography; D001562:Benzimidazoles / Q000378:metabolism / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000378:metabolism / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000502:physiology*; D008297:Male; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000145:classification / Q000378:metabolism; D013777:Tetrazoles / Q000378:metabolism / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; C077793:candesartan cilexetil; C081643:candesartan