| RRC ID |
6519
|
| Author |
Ahmed M, Muntasir HA, Hossain M, Ishiguro M, Komiyama T, Muramatsu I, Kurose H, Nagatomo T.
|
| Title |
Beta-blockers show inverse agonism to a novel constitutively active mutant of beta1-adrenoceptor.
|
| Journal |
J Pharmacol Sci
|
| 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.
|
| Volume |
102(2)
|
| Pages |
167-72
|
| Published |
2006-10-1
|
| DOI |
10.1254/jphs.fp0060640
|
| PII |
JST.JSTAGE/jphs/FP0060640
|
| PMID |
17031074
|
| MeSH |
Adrenergic beta-1 Receptor Agonists*
Adrenergic beta-Antagonists / pharmacology*
Cell Line
Cyclic AMP / metabolism
Humans
Ligands
Point Mutation*
Protein Binding
Receptors, Adrenergic, beta-1 / genetics*
|
| IF |
2.835
|
| Times Cited |
7
|
|
WOS Category
|
PHARMACOLOGY & PHARMACY
|
| Resource |
| Human and Animal Cells |
|
