Comparative functional properties of two structurally similar selective nonpeptide drug-like ligands for the angiotensin II type-2 (AT2) receptor. Effects on neurite outgrowth in NG108-15 cells

2013 ◽  
Vol 699 (1-3) ◽  
pp. 160-171 ◽  
Author(s):  
Marie-Odile Guimond ◽  
Charlotta Wallinder ◽  
Mathias Alterman ◽  
Anders Hallberg ◽  
Nicole Gallo-Payet
Keyword(s):  
Angiotensin Ii ◽  
Neurite Outgrowth ◽  
Functional Properties ◽  
At2 Receptor

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

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 Candesartan Cilexetil Improves Angiotensin II Type 2 Receptor-Mediated Neurite Outgrowth via the PI3K-Akt Pathway in Fructose-Induced Insulin-Resistant Rats

Diabetes ◽  
2012 ◽  
Vol 61 (4) ◽  
pp. 925-932 ◽  
Author(s):  
N. Hashikawa-Hobara ◽  
N. Hashikawa ◽  
Y. Inoue ◽  
H. Sanda ◽  
Y. Zamami ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Neurite Outgrowth ◽  
Candesartan Cilexetil ◽  
Akt Pathway ◽  
Insulin Resistant

scholarly journals Direct Stimulation of Angiotensin II Type 2 Receptor Enhances Spatial Memory

2011 ◽  
Vol 32 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Fei Jing ◽  
Masaki Mogi ◽  
Akiko Sakata ◽  
Jun Iwanami ◽  
Kana Tsukuda ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Angiotensin Ii ◽  
Neurite Outgrowth ◽  
Hippocampal Neurons ◽  
Receptor Agonist ◽  
Laser Speckle ◽  
Morris Water Maze Test ◽  
Direct Stimulation ◽  
Stimulation Of

We examined the possibility that direct stimulation of the angiotensin II type 2 (AT2) receptor by a newly generated direct AT2 receptor agonist, Compound 21 (C21), enhances cognitive function. Treatment with C21 intraperitoneal injection for 2 weeks significantly enhanced cognitive function evaluated by the Morris water maze test in C57BL6 mice, but this effect was not observed in AT2 receptor-deficient mice. However, C21-induced cognitive enhancement in C57BL6 mice was attenuated by coadministration of icatibant, a bradykinin B2 receptor antagonist. Administration of C21 dose dependently increased cerebral blood flow assessed by laser speckle flowmetry and hippocampal field-excitatory postsynaptic potential (f-EPSP) determined by electrophysiological techniques in C57BL6 mice. Furthermore, activation of the AT2 receptor by C21 promoted neurite outgrowth of cultured hippocampal neurons prepared from fetal transgenic mice expressing green fluorescent protein. Finally, we investigated the pathologic relevance of C21 for spatial learning using an Alzheimer's disease mouse model with intracerebroventricular injection of amyloid-β (1 to 40). We observed that treatment with C21 prevented cognitive decline in this model. These results suggest that a direct AT2 receptor agonist, C21, enhances cognitive function at least owing to an increase in CBF, enhancement of f-EPSP, and neurite outgrowth in hippocampal neurons.

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.

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