Shin-Ichiro Miura

Fukuoka University, Hukuoka, Fukuoka, Japan

Are you Shin-Ichiro Miura?

Claim your profile

Publications (3)5.06 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The present study investigated the internalization behavior of the constitutively active mutant (CAM) N111G of angiotensin II type 1 (AT(1)) receptor and correlated the result with the mechanism of the constitutive activity of the mutant. The inverse agonist activity of valsartan, losartan, candesartan, and telmisartan was also examined by inositol phosphate (IP) accumulation study as well as receptor-internalization assay. Both wild-type (WT) and N111G mutant receptors were transiently expressed in COS-7 cells and the binding affinities towards the agonist and these four AT(1) antagonists were determined. Production of total IP was measured in the presence and absence of the compounds. The agonist-induced receptor internalization of both WT and N111G mutant receptors was also investigated. Although the mutant showed similar binding characteristics with agonist and the antagonists used as WT, the internalization of the mutant was much lower (19.56 +/- 2.87%) than that of the WT receptor (74.63 +/- 1.00%). Internalization of the mutant significantly increased (63.22 +/- 0.03%) in the presence of valsartan, which also showed significant inverse agonist activity in the N111G mutant. The results indicate that internalization of CAM N111G of the AT(1) receptor is induced by the use of valsartan, which may be an important characteristic of inverse agonist activities of AT(1) antagonists in N111G.
    Full-text · Article · Oct 2009 · Journal of Pharmacological Sciences
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study was designed to examine the importance of interaction in the binding of selective angiotensin II receptor antagonists to angiotensin II type 1 receptor using molecular modeling. The AT(1) antagonists used in this study were valsartan, candesartan and losartan. AT(1) receptor structural model was constructed by homology modeling using structural models of rhodopsin photointermediates. Through molecular modeling, possible binding sites for these drugs were suggested to lie between transmembrane domains (TM) 3, 5, and 6 of AT(1) receptor. The carboxylic acid group and tetrazole ring of valsartan possibly interact with Lys199 of TM5 and Ser109 of TM3 and Asn295 of TM7 of AT(1) receptor, respectively. In candesartan, carboxylic group, tetrazole ring, and ethoxy group oxygen possibly interact with Lys199 of TM5, Ser109 of TM3 and Asn295 of TM7 and Gln257 of TM6, respectively. In losartan, tetrazole ring and hydroxymethyl group possibly interact with Asn295 of TM7 and Ser109 of TM3, respectively. The results of the present study suggested that candesartan interacts at a higher number of binding sites compared to valsartan whereas losartan has a lower number of binding sites with the amino acid residues of the AT(1) receptor. These findings are consistent with the data of the radioligand-binding studies of the antagonists with the AT(1) receptor.
    Full-text · Article · Jun 2009 · Life sciences

  • No preview · Conference Paper · Sep 2008