The angiotensin II type 2 (AT2) receptor: an enigmatic seven transmembrane receptor

10.2741/3289 ◽  
2009 ◽  
Vol Volume (14) ◽  
pp. 958 ◽  
Author(s):  
Enzo, R. Porrello
Keyword(s):  
Angiotensin Ii ◽  
At2 Receptor

Protective effects of the angiotensin II AT2 receptor agonist compound 21 in ischemic stroke: a nose-to-brain delivery approach

2018 ◽  
Vol 132 (5) ◽  
pp. 581-593 ◽  
Author(s):  
Douglas M. Bennion ◽  
Chad H. Jones ◽  
Alex N. Dang ◽  
Jacob Isenberg ◽  
Justin T. Graham ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Angiotensin Ii ◽  
Receptor Agonist ◽  
At2 Receptor ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Receptor Agonists ◽  
Compound 21 ◽  
Neuroprotective Actions

Significant neuroprotective effects of angiotensin II type 2 (AT2) receptor (AT2 receptor) agonists in ischemic stroke have been previously demonstrated in multiple studies. However, the routes of agonist application used in these pre-clinical studies, direct intracerebroventricular (ICV) and systemic administration, are unsuitable for translation into humans; in the latter case because AT2 receptor agonists are blood–brain barrier (BBB) impermeable. To circumvent this problem, in the current study we utilized the nose-to-brain (N2B) route of administration to bypass the BBB and deliver the selective AT2 receptor agonist Compound 21 (C21) to naïve rats or rats that had undergone endothelin 1 (ET-1)-induced ischemic stroke. The results obtained from the present study indicated that C21 applied N2B entered the cerebral cortex and striatum within 30 min in amounts that are therapeutically relevant (8.4–9 nM), regardless of whether BBB was intact or disintegrated. C21 was first applied N2B at 1.5 h after stroke indeed provided neuroprotection, as evidenced by a highly significant, 57% reduction in cerebral infarct size and significant improvements in Bederson and Garcia neurological scores. N2B-administered C21 did not affect blood pressure or heart rate. Thus, these data provide proof-of-principle for the idea that N2B application of an AT2 receptor agonist can exert neuroprotective actions when administered following ischemic stroke. Since N2B delivery of other agents has been shown to be effective in certain human central nervous system diseases, the N2B application of AT2 receptor agonists may become a viable mode of delivering these neuroprotective agents for human ischemic stroke patients.

scholarly journals Involvement of Protein Kinase Cα (PKCα) in the Early Action of Angiotensin II Type 2 (AT2) Effects on Neurite Outgrowth in NG108–15 Cells: AT2-Receptor Inhibits PKCα and p21ras Activity

Endocrinology ◽  
2006 ◽  
Vol 147 (9) ◽  
pp. 4263-4272 ◽  
Author(s):  
Hélène Beaudry ◽  
Louis Gendron ◽  
Marie-Odile Guimond ◽  
Marcel D. Payet ◽  
Nicole Gallo-Payet
Keyword(s):  
Angiotensin Ii ◽  
Protein Kinase ◽  
Neurite Outgrowth ◽  
At2 Receptor ◽  
Early Action ◽  
Protein Kinase Cα

scholarly journals Ontogeny of angiotensin II type 2 (AT2) receptor mRNA in the rat

1995 ◽  
Vol 47 (4) ◽  
pp. 1095-1100 ◽  
Author(s):  
Sadoutounissa Shanmugam ◽  
Zsolt G. Lenkei ◽  
Jean-Marie R. Gasc ◽  
Pierre L. Corvol ◽  
Catherine M. Llorens-Cortes
Keyword(s):  
Angiotensin Ii ◽  
At2 Receptor ◽  
Receptor Mrna

scholarly journals The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: gain-of-function study using gene transfer.

1995 ◽  
Vol 92 (23) ◽  
pp. 10663-10667 ◽  
Author(s):  
M. Nakajima ◽  
H. G. Hutchinson ◽  
M. Fujinaga ◽  
W. Hayashida ◽  
R. Morishita ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Gene Transfer ◽  
At1 Receptor ◽  
At2 Receptor ◽  
Gain Of Function ◽  
Growth Effects ◽  
Function Study

Upregulation of angiotensin II type 2 receptor expression in estrogen-induced pituitary hyperplasia

2004 ◽  
Vol 286 (5) ◽  
pp. E786-E794 ◽  
Author(s):  
Cecilia Suarez ◽  
Graciela Díaz-Torga ◽  
Arturo González-Iglesias ◽  
Carolina Cristina ◽  
Damasia Becu-Villalobos
Keyword(s):  
Angiotensin Ii ◽  
Receptor Expression ◽  
Receptor Subtype ◽  
At2 Receptor ◽  
Ang Ii ◽  
Pituitary Hyperplasia ◽  
Releasing Effect ◽  
At2 Receptors

Recent evidence shows that reexpression and upregulation of angiotensin II (ANG II) type 2 (AT2) receptor in adult tissues occur during pathological conditions such as tissue hyperplasia, inflammation, and remodeling. In particular, expression of functional AT2 receptors in the pituitary and their physiological significance and regulation have not been described. In this study, we demonstrate that chronic in vivo estrogen treatment, which induces pituitary hyperplasia, enhances local AT2 expression (measured by Western blot and RT-PCR) concomitantly with downregulation of ANG II type 1 (AT1) receptors. In vivo progesterone treatment of estrogen-induced pituitary hyperplasia did not modify either the ANG II receptor subtype expression pattern or octapeptide-induced and AT1-mediated calcium signaling. Nevertheless, an unexpected potentiation of the ANG II prolactin-releasing effect was observed in this group, and this response was sensitive to both AT1 and AT2 receptor antagonists. These data are the first to document that ANG II can act at the pituitary level through the AT2 receptor subtype and that estrogens display a differential regulation of AT1 and AT2 receptors at this level.

scholarly journals Regulation of Vascular Proteoglycan Synthesis by Angiotensin II Type 1 and Type 2 Receptors

2001 ◽  
Vol 12 (12) ◽  
pp. 2609-2615
Author(s):  
Ryoko Shimizu-Hirota ◽  
Hiroyuki Sasamura ◽  
Mizuo Mifune ◽  
Hideaki Nakaya ◽  
Mari Kuroda ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Proteoglycan Synthesis ◽  
At2 Receptor ◽  
Receptor Stimulation ◽  
Epidermal Growth

ABSTRACT. Recent studies have shown that proteoglycans play an important role in the development of vascular disease and renal failure. In this study, the effects of angiotensin II (AngII) type 1 (AT1) and type 2 (AT2) receptor stimulation on glycosaminoglycan and proteoglycan core protein synthesis in vascular smooth muscle cells (VSMC) were examined. Treatment of AT1 receptor-expressing VSMC with AngII resulted in a dose-dependent and time-dependent increase (2- to 4-fold) in 3H-glucosamine/35S-sulfate incorporation, which was abolished by pretreatment with the AT1 receptor antagonist, losartan. The effects of AngII were inhibited by the epidermal growth factor receptor inhibitor, AG1478, and the mitagen-activated protein kinase kinase inhibitor, PD98059, but not the protein kinase C inhibitors, chelerythrine and staurosporine. AngII treatment also resulted in significant increases in the mRNA of the core proteins, versican, biglycan, and perlecan. The effects of AT2 receptor stimulation were examined by retroviral transfection of VSMC with the AT2 receptor. Stimulation of the AT2 receptor in these VSMC-AT2 cells resulted in a significant (1.3-fold) increase in proteoglycan synthesis, which was abolished by the AT2 receptor antagonist, PD123319, and attenuated by pretreatment with pertussis toxin. These results implicate both AT1 and AT2 receptors in the regulation of proteoglycan synthesis and suggest the involvement of epidermal growth factor receptor-dependent tyrosine kinase pathways and Gαi/o-mediated mechanisms in the effects of the two receptors.

scholarly journals Reduced Expression of Antihypertensive Angiotensin II Type 2 (AT2) Receptor in the kidney and cultured mesangial cells from Stroke-Prone SHR

1997 ◽  
Vol 38 (4) ◽  
pp. 563-563
Author(s):  
Masahisa Goto ◽  
Masashi Mukoyama ◽  
Issei Tanaka ◽  
Tsunekazu Matsumoto ◽  
Masayo Nakagawa ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Mesangial Cells ◽  
At2 Receptor
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