Detail of "37827-06-8"

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Angiotensin-induced changes in the apparent size of rat liver angiotensin receptors

Angiotensin-induced changes in the apparent size of rat liver angiotensin receptors. Guillemette, G.; Guillon, G.; Marie, J.; Pantaloni, C.; Balestre, M. N.; Escher, E.; Jard, S. (Cent. CNRS-INSERM Pharmacol.-Endocrinol., Montpellier 34033, Fr.). J. Recept. Res., 4(1-6), 267-81 (English) 1984. CODEN: JRERDM. ISSN: 0197-5110. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Angiotensin II [11128-99-7] receptors from rat liver were labeled using 4 different ligands: 3H-labeled (Sar1-Ile5)-Angiotensin II (SarAII) [51833-69-3], 3H-labeled (Sar1-Ile5-Ile8)-Angiotensin II (SarIleAII) [37827-06-8], 125I-labeled (Sar1-Ile5-(4'-N3)Phe8)-Angiotensin II (IN3AII) [87262-02-0], and 125I-labeled (Sar1-Ile5-(4'-N3)D-Phe8)-Angiotensin II (IN3DPheAII) [95976-57-1]. SarAII and IN3AII behaved like agonists and SarIleAII and IN3DPheAII like antagonists. All 4 ligands labeled the same population of sites. The azido derivs. allowed covalent labeling of receptors with a high yield (about 40%). Membranes were solubilized by Triton X-100 under exptl. conditions which ensured complete solubilization of the liganded receptors in a stable form (less than 40% dissocn. after 20 h). The apparent size of liganded angiotensin receptors was detd. by gel filtration on Ultrogel ACA-34 columns and by SDS gel electrophoresis (in the case of covalent labeling). The apparent Stokes radius of solubilized angiotensin receptors depended on whether the receptor was labeled with an agonist (Stokes radius = 6.2 nm after labeling with SarAII) or with an antagonist (Stokes radii of 5.5 nm and 5.6 nm after labeling with SarIleAII and IN3DPheAII, resp.). After covalent labeling with IN3AII, angiotensin receptors were eluted as a mix. of light and heavy forms. SDS gel electrophoresis revealed only 1 mol. entity of Mr 64,000. Thus, binding of an agonist to liver angiotensin receptors triggers or stabilizes an interaction with another membrane component involved in the coupling of the receptor to its primary effector.

On the mechanisms of action of two classes of angiotensin antagonists at smooth muscle receptors

On the mechanisms of action of two classes of angiotensin antagonists at smooth muscle receptors. Moore, G. J.; Matsoukas, J. M.; Scanlon, M. N.; Franklin, K. J.; Goghari, M. H. (Dep. Med. Biochem., Univ. Calgary, Calgary, AB T2N 1N4, Can.). Proc. West. Pharmacol. Soc., 27, 377-83 (English) 1984. CODEN: PWPSA8. ISSN: 0083-8969. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Angiotensin II (Ang II) [4474-91-3] actions on isolated rat uteri were antagonized by [Sar1, Tyr(Me)4]Ang II (I) [88874-29-7], [Sar1, Tyr(Me)4, Ile2]Ang II (II) [92780-94-4], and [Sar1,Ile8]Ang II (III) [37827-06-8]. The in vivo antagonist potencies of I and III were also detd. in a rat pressor assay. In the uterine assay, the blocking concns. of I and II required to reduce the response to the ED50 of Ang II to the response of an ED50/2 dose were readily established and the effects of both antagonists were completely reversible within 12 min. The actions of III differed from that of the 2 competitive agonists. It was not possible to obtain a meaningful blocking concn. of III since III incapacitated the ability of the uterus to respond to Ang II for >2 h and Ang II was unable to displace III from all the receptors sites. Thus, III acted as a noncompetitive antagonist. It was also a noncompetitive antagonist in the pressor assay. The effect of structures on activity was discussed. From these results and others a model was proposed for angiotensin action at smooth muscle receptors. The model depicts the functionally active domains of the mol.; a catalytic site and an accessory site, and their compn. and interactions with the receptor are discussed.