Interaction between Angiotensin Receptor and β-Adrenergic Receptor Regulates the Production of Amyloid β-Protein.
Alzheimer's disease (AD) is characterized by the formation of extracellular amyloid plaques containing the amyloid β-protein (Aβ) within the parenchyma of the brain. Aβ 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 Aβ production, and that telmisartan (Telm), which is an angiotensin II receptor blocker (ARB), increased Aβ production via AT1R. However, the precise mechanism underlying how AT1R is involved in Aβ production is unknown. Interestingly, AT1R, a G protein-coupled receptor, was strongly suggested to be involved in signal transduction by heterodimerization with β2-adrenergic receptor (β2-AR), which is also shown to be involved in Aβ generation. Therefore, in this study, we aimed to clarify whether the interaction between AT1R and β2-AR is involved in the regulation of Aβ production. To address this, we analyzed whether the increase in Aβ production by Telm treatment is affected by β-AR antagonist using fibroblasts overexpressing amyloid precursor protein (APP). We found that the increase in Aβ production by Telm treatment was decreased by the treatment of β2-AR selective antagonist ICI-118551 more strongly than the treatment of β1-AR selective antagonists. Furthermore, deficiency of AT1R abolished the effect of β2-AR antagonist on the stimulation of Aβ production caused by Telm. Taken together, the interaction between AT1R and β2-AR is likely to be involved in Aβ production.
['Kikuchi|Kota|K|', 'Fujita|Yu|Y|', 'Shen|Xuefeng|X|', 'Liu|Junjun|J|', 'Terakawa|Tomoki|T|', 'Nishikata|Daiki|D|', 'Niibori|Sho|S|', 'Ito|Takayuki|T|', 'Ashidate|Kazuyuki|K|', 'Kikuchi|Takuya|T|', 'Kikuchi|Yu|Y|', 'Maeda|Tomoji|T|', 'Zou|Kun|K|', 'Komano|Hiroto|H|']
D000319:Adrenergic beta-Antagonists D016229:Amyloid beta-Peptides D047228:Angiotensin II Type 1 Receptor Blockers D000818:Animals D001262:Atenolol D017298:Bisoprolol D002478:Cells, Cultured D008810:Mice, Inbred C57BL D011412:Propanolamines D011433:Propranolol D044140:Receptor, Angiotensin, Type 1 D018343:Receptors, Adrenergic, beta-2 D000077333:Telmisartan
angiotensin receptor amyloid β-protein Alzheimer’s disease adrenergic receptor