Role of βarrestin1 in AT1R‐mediated mitogen‐activated protein kinase activation in Wistar and SHR brainstem astrocytes

In astrocytes, the effects of beta arrestin ( βarr) in angiotensin (Ang) type 1 receptor (AT1R) signaling remains unknown. A combination of pharmacological ([Sar1, Il4, Il8] Ang ‐II, SII) and gene manipulation approaches were used to investigate the role of βarrs in AT1R ‐mediated signaling in isolated brainstem spontaneously hypertensive rats (SHRs) and Wistar rats astrocytes. We found that βarr1 is the predominant arrestin isoform at the protein level in brainstem astrocytes. Ang II mediates activation of mitogen‐activated protein kinases (MAPKs) through βar r1 in brainstem astrocytes. This effect is dampened in SHR brainstem astrocytes suggesting a role for βarr in this model. Abstractβarrestin (βarr)‐1 and ‐2 are ubiquitously (outside the retina) expressed G‐protein‐coupled receptor adapter proteins. They uncouple G‐protein‐coupled receptors from G proteins, internalize the receptor, and subsequently initiate their own wave of signaling independently of G proteins. Angiotensin (Ang) II type 1 receptor (AT1R) is a well ‐established example of a receptor signaling through βarrs. Despite the pivotal role of brain AT1Rs in the regulation of blood pressure, the involvement of βarr‐dependent signaling, mediated by AT1Rs is not well studied. Particularly, in brain astrocytes very little is known about the effects of βarrs in AT1R signaling. Herein, we utilized a combination of pharmacological and gene manipulation approaches to investigate the rol...
Source: Journal of Neurochemistry - Category: Neurology Authors: Tags: Original Article Source Type: research