Beta-blockers show inverse agonism to a novel constitutively active mutant of beta1-adrenoceptor.
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.
Ahmed
Maruf
M
Pharmacy Department, University of Rajshahi, Bangladesh.
Muntasir
Habib Abul
HA
Hossain
Murad
M
Ishiguro
Masaji
M
Komiyama
Tadazumi
T
Muramatsu
Ikunobu
I
Kurose
Hitoshi
H
Nagatomo
Takafumi
T
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*
D058665:Adrenergic beta-1 Receptor Agonists; D000319:Adrenergic beta-Antagonists; D008024:Ligands; D018342:Receptors, Adrenergic, beta-1; D000242:Cyclic AMP