title: Molecular characterization of pharmacological properties and selectivity of SWR-0315NA for beta3-adrenoceptors.
abstract: The pharmacological properties of SWR-0315NA, (E,Z)-[4[[1-[2-[(3-phenoxy-2-hydroxy propyl)]amino]ethyl]-1-propenyl]phenoxy]acetic acid sodium, were compared with those of (-)-isoproterenol. In the radioligand binding studies of [(125)I]iodocyanopindolol with COS-7 cell membranes that transiently expressed human beta-adrenoceptor (beta-AR) subtypes, SWR-0315NA exhibited 1-fold and 2-fold greater binding affinities for beta(3)-AR than those for beta(1)- and beta(2)-ARs, respectively. The maximal stimulatory effects of SWR-0315NA on cAMP accumulation in CHO cells expressing all the beta-AR subtypes were 79%, 3% and 93% for beta(1)-, beta(2)- and beta(3)-ARs of those produced by (-)-isoproterenol, respectively. SWR-0315NA has 26.3-fold and more than 630-fold greater selectivity for beta(3)-AR than those for beta(1)- and beta(2)-ARs in potency, respectively. These results indicate that although SWR-0315NA has lower binding selectivity towards beta-AR subtypes, it is a selective agonist with high intrinsic activity for beta(3)-AR as compared with (-)-isoproterenol.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Japan.
authors.forename: Maruf
authors.initials: M
authors.lastname: Ahmed
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hanaoka
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kiso
authors.forename: Takao
authors.initials: T
authors.lastname: Kakita
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ohtsubo
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nagatomo
mesh_terms: D000085:Acetates / Q000737:chemistry* / Q000494:pharmacology*; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D007545:Isoproterenol / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism
chemical_list: D000085:Acetates; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D022702:Receptors, Adrenergic, beta-3; C401286:SWR 0342SA; D007545:Isoproterenol