title: Beta-blockers show inverse agonism to a novel constitutively active mutant of beta1-adrenoceptor.
abstract: We obtained a new mutant of the beta(1)-adrenergic receptor (beta(1)-AR) by point mutations that can constitutively activate beta(1)-AR. Aspartate104 of the beta(1)-AR in the 2nd transmembrane was replaced with alanine. The beta(1)-AR mutant expressed in human embryonic kidney (HEK)-293 cells displayed high level of constitutive activity with respect to wild-type (P<0.05), which could be partially inhibited by some beta-blockers. The constitutive activity of the mutant was confirmed by the finding that the enhanced activity is dependent on the level of receptor expression. The results of this study might have interesting implications for future studies aiming at elucidating the activation process of the beta(1)-AR as well as the mechanism of action of beta-blockers.
authors.affiliation: Pharmacy Department, University of Rajshahi, Bangladesh.
authors.forename: Maruf
authors.initials: M
authors.lastname: Ahmed
authors.forename: Habib Abul
authors.initials: HA
authors.lastname: Muntasir
authors.forename: Murad
authors.initials: M
authors.lastname: Hossain
authors.forename: Masaji
authors.initials: M
authors.lastname: Ishiguro
authors.forename: Tadazumi
authors.initials: T
authors.lastname: Komiyama
authors.forename: Ikunobu
authors.initials: I
authors.lastname: Muramatsu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurose
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nagatomo
mesh_terms: D058665:Adrenergic beta-1 Receptor Agonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D008024:Ligands; D017354:Point Mutation; D011485:Protein Binding; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D000319:Adrenergic beta-Antagonists; D008024:Ligands; D018342:Receptors, Adrenergic, beta-1; D000242:Cyclic AMP