| First Author | Kikuchi K | Year | 2020 |
| Journal | Biol Pharm Bull | Volume | 43 |
| Issue | 4 | Pages | 731-735 |
| PubMed ID | 32238715 | Mgi Jnum | J:298516 |
| Mgi Id | MGI:6480205 | Doi | 10.1248/bpb.b20-00007 |
| Citation | Kikuchi K, et al. (2020) Interaction between Angiotensin Receptor and beta-Adrenergic Receptor Regulates the Production of Amyloid beta-Protein. Biol Pharm Bull 43(4):731-735 |
| abstractText | Alzheimer's disease (AD) is characterized by the formation of extracellular amyloid plaques containing the amyloid beta-protein (Abeta) within the parenchyma of the brain. Abeta is considered to be the key pathogenic factor of AD. Recently, we showed that Angiotensin II type 1 receptor (AT1R), which regulates blood pressure, is involved in Abeta production, and that telmisartan (Telm), which is an angiotensin II receptor blocker (ARB), increased Abeta production via AT1R. However, the precise mechanism underlying how AT1R is involved in Abeta production is unknown. Interestingly, AT1R, a G protein-coupled receptor, was strongly suggested to be involved in signal transduction by heterodimerization with beta2-adrenergic receptor (beta2-AR), which is also shown to be involved in Abeta generation. Therefore, in this study, we aimed to clarify whether the interaction between AT1R and beta2-AR is involved in the regulation of Abeta production. To address this, we analyzed whether the increase in Abeta production by Telm treatment is affected by beta-AR antagonist using fibroblasts overexpressing amyloid precursor protein (APP). We found that the increase in Abeta production by Telm treatment was decreased by the treatment of beta2-AR selective antagonist ICI-118551 more strongly than the treatment of beta1-AR selective antagonists. Furthermore, deficiency of AT1R abolished the effect of beta2-AR antagonist on the stimulation of Abeta production caused by Telm. Taken together, the interaction between AT1R and beta2-AR is likely to be involved in Abeta production. |
