scholarly journals Immunohistochemical Localization ofAT1a,AT1b, andAT2Angiotensin II Receptor Subtypes in the Rat Adrenal, Pituitary, and Brain with a Perspective Commentary

2013 ◽  
Vol 2013 ◽  
pp. 1-22 ◽  
Author(s):  
Courtney Premer ◽  
Courtney Lamondin ◽  
Ann Mitzey ◽  
Robert C. Speth ◽  
Mark S. Brownfield
Keyword(s):  
Angiotensin Ii ◽  
Area Postrema ◽  
Zona Glomerulosa ◽  
Immunohistochemical Localization ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Multivesicular Bodies ◽  
Sodium Appetite ◽  
Endocytic Vesicles ◽  
The Brain

Angiotensin II increases blood pressure and stimulates thirst and sodium appetite in the brain. It also stimulates secretion of aldosterone from the adrenal zona glomerulosa and epinephrine from the adrenal medulla. The rat has 3 subtypes of angiotensin II receptors:AT1a,AT1b, and AT2. mRNAs for all three subtypes occur in the adrenal and brain. To immunohistochemically differentiate these receptor subtypes, rabbits were immunized with C-terminal fragments of these subtypes to generate receptor subtype-specific antibodies. Immunofluorescence revealedAT1aand AT2receptors in adrenal zona glomerulosa and medulla.AT1bimmunofluorescence was present in the zona glomerulosa, but not the medulla. Ultrastructural immunogold labeling for theAT1areceptor in glomerulosa and medullary cells localized it to plasma membrane, endocytic vesicles, multivesicular bodies, and the nucleus.AT1band AT2, but notAT1a, immunofluorescence was observed in the anterior pituitary. Stellate cells wereAT1bpositive while ovoid cells were AT2positive. In the brain, neurons wereAT1a,AT1b, and AT2positive, but glia was onlyAT1bpositive. Highest levels ofAT1a,AT1b, and AT2receptor immunofluorescence were in the subfornical organ, median eminence, area postrema, paraventricular nucleus, and solitary tract nucleus. These studies complement those employing different techniques to characterize Ang II receptors.

Distribution of α1-adrenoceptor subtype proteins in different tissues of neonatal and adult rats

2000 ◽  
Vol 78 (3) ◽  
pp. 237-243 ◽  
Author(s):  
Hao Shen ◽  
Krishna G Peri ◽  
Xing-Fei Deng ◽  
Sylvain Chemtob ◽  
Daya R Varma
Keyword(s):  
Vas Deferens ◽  
Polyclonal Antibodies ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Rat Tissues ◽  
Adult Rats ◽  
Adult Rat ◽  
Old Rats ◽  
Kidney Liver ◽  
The Brain

Distribution of α1-adrenoceptor (α1AR) subtype (α1A, α1B, α1D) proteins in brain, heart, kidney, and liver of 1-week-old rats and in brain, heart, aorta, kidney, liver, vas deferens, prostate, and adrenal glands of adult rats was investigated by Western analysis, using receptor subtype specific polyclonal antibodies. High levels of immunoreactive α1AAR and α1DAR in brain and heart and of α1BAR in liver and heart of neonatal rats were detected. In adult rat tissues, the abundance of α1AAR protein was most marked in the brain, intermediate in heart, aorta, liver, vas deferens, and adrenals, and minimal in the kidney and prostate; relative to other tissues, the expression of α1BAR was higher in brain and heart and that of α1DAR in brain. All the three receptor subtypes increased with age in the brain cortex, whereas the abundance of α1BAR increased in the heart but decreased in the liver; α1AAR and α1DAR in liver, kidney, and heart were not affected by age. It is concluded that α1AR subtypes are widely expressed in different neonatal and adult rat tissues.Key words: α1A-adrenoceptors, α1B-adrenoceptors, α1D-adrenoceptors, α1-adrenoceptor proteins.

Two Sites of Cardiovascular Action of Angiotensin II in the Brain of the Dog

1973 ◽  
Vol 44 (4) ◽  
pp. 417-420 ◽  
Author(s):  
P. L. Gildenberg ◽  
C. M. Ferrario ◽  
J. W. McCubbin
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Lateral Ventricle ◽  
Area Postrema ◽  
Pressor Response ◽  
Cerebral Ventricle ◽  
Vertebral Arteries ◽  
Adjacent Structures ◽  
The Brain ◽  
Lateral Cerebral Ventricle

1. Infusion of angiotensin into both vertebral arteries or into a lateral cerebral ventricle of dogs anaesthetized with morphine-chloralose elicited a centrally mediated rise in blood pressure. 2. Heat coagulation of the area postrema and immediately adjacent structures abolished the pressor response to infusion of angiotensin into the circulation of the vertebral arteries, but did not alter the pressor response when the peptide was delivered into a cerebral lateral ventricle; transection of the midbrain eliminated the latter response but not the former. 3. It is concluded that there are at least two areas in the dog's brain that respond to angiotensin by inducing a raised blood pressure.

scholarly journals Regulation of angiotensin II receptors and extracellular matrix turnover in human retinal pigment epithelium: role of angiotensin II

2008 ◽  
Vol 295 (6) ◽  
pp. C1633-C1646 ◽  
Author(s):  
Gary E. Striker ◽  
Francoiçe Praddaude ◽  
Oscar Alcazar ◽  
Scott W. Cousins ◽  
Maria E. Marin-Castaño
Keyword(s):  
Extracellular Matrix ◽  
Angiotensin Ii ◽  
Type Iv Collagen ◽  
Pigment Epithelium ◽  
Receptor Expression ◽  
Age Related Macular Degeneration ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Type Iv

The early stage of age-related macular degeneration (AMD) is characterized by the formation of subretinal pigment epithelium (RPE) deposits as a result of the dysregulation in the turnover of extracellular matrix (ECM) molecules. However, the mechanism involved remains unclear. Hypertension (HTN) is an important risk factor for AMD, and angiotensin II (ANG II) is the most important hormone associated with HTN. However, the relevance of ANG II receptors and ANG II effects on RPE have not been investigated yet. Therefore, the expression and regulation of ANG II receptors as well as the ECM turnover were studied in human RPE. ANG II receptors were expressed and upregulated by ANG II in human RPE. This regulation resulted in functional receptor expression, since an increase in intracellular concentration of calcium was observed upon ANG II stimulation. ANG II also increased matrix metalloproteinase (MMP)-2 activity and MMP-14 at the mRNA and protein levels as well as type IV collagen degradation. These ANG II effects were abolished in the presence of the ANG II receptor subtype 1 (AT1) receptor antagonist candesartan. In contrast, ANG II decreased type IV collagen via both AT1 and AT2 receptors, suggesting a synergistic effect of the two receptor subtypes. In conclusion, we have confirmed the presence of ANG II receptors in human RPE and their regulation by ANG II as well as the regulation of ECM molecules via ANG II receptors. Our data support the hypothesis that ANG II may exert biological function in RPE through ANG II receptors and that ANG II may cause dysregulation of molecules that play a major role in the turnover of ECM in RPE basement membrane and Bruch's membrane, suggesting a pathogenic mechanism to explain the link between HTN and AMD.

Angiotensin-II Stimulates DNA Synthesis in rat adrenal zona glomerulosa cells: Receptor subtypes involved and possible signal transduction mechanism

1997 ◽  
Vol 23 (3) ◽  
pp. 191-203 ◽  
Author(s):  
Giuseppina Mazzocchi ◽  
Ludwik K. Malendowicz ◽  
Giuseppe Gottardo ◽  
Piera Rebuffat ◽  
Gastone G. Nussdorfer
Keyword(s):  
Signal Transduction ◽  
Angiotensin Ii ◽  
Dna Synthesis ◽  
Zona Glomerulosa ◽  
Receptor Subtypes ◽  
Transduction Mechanism ◽  
Signal Transduction Mechanism ◽  
Glomerulosa Cells ◽  
Zona Glomerulosa Cells

scholarly journals Angiotensin II-Induced Mitogen-Activated Protein Kinase Phosphatase-1 Expression in Bovine Adrenal Glomerulosa Cells: Implications in Mineralocorticoid Biosynthesis

Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5573-5581 ◽  
Author(s):  
Andrés J. Casal ◽  
Stéphane Ryser ◽  
Alessandro M. Capponi ◽  
Carine F. Wang-Buholzer
Keyword(s):  
Angiotensin Ii ◽  
Mapk Pathway ◽  
Fold Increase ◽  
Zona Glomerulosa ◽  
Mitogen Activated Protein Kinase ◽  
Receptor Subtype ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Aldosterone Production ◽  
Glomerulosa Cells

Angiotensin II (AngII) stimulates aldosterone biosynthesis in the zona glomerulosa of the adrenal cortex. AngII also triggers the MAPK pathways (ERK1/2 and p38). Because ERK1/2 phosphorylation is a transient process, phosphatases could play a crucial role in the acute steroidogenic response. Here we show that the dual specificity (threonine/tyrosine) MAPK phosphatase-1 (MKP-1) is present in bovine adrenal glomerulosa cells in primary culture and that AngII markedly increases its expression in a time- and concentration-dependent manner (IC50 = 1 nm), a maximum of 548 ± 10% of controls being reached with 10 nm AngII after 3 h (n = 3, P < 0.01). This effect is completely abolished by losartan, a blocker of the AT1 receptor subtype. Moreover, this AngII-induced MKP-1 expression is reduced to 250 ± 35% of controls (n = 3, P < 0.01) in the presence of U0126, an inhibitor of ERK1/2 phosphorylation, suggesting an involvement of the ERK1/2 MAPK pathway in MKP-1 induction. Indeed, shortly after AngII-induced phosphorylation of ERK1/2 (220% of controls at 30 min), MKP-1 protein expression starts to increase. This increase is associated with a reduction in ERK1/2 phosphorylation, which returns to control values after 3 h of AngII challenge. Enhanced MKP-1 expression is essentially due to a stabilization of MKP-1 mRNA. AngII treatment leads to a 53-fold increase in phosphorylated MKP-1 levels and a doubling of MKP-1 phosphatase activity. Overexpression of MKP-1 results in decreased phosphorylation of ERK1/2 and aldosterone production in response to AngII stimulation. These results strongly suggest that MKP-1 is the specific phosphatase induced by AngII and involved in the negative feedback mechanism ensuring adequate ERK1/2-mediated aldosterone production in response to the hormone.

The Role of Endogenous Opiates in the Area Postrema Pressor Pathway

1980 ◽  
Vol 59 (s6) ◽  
pp. 267s-269s ◽  
Author(s):  
Julianna E. Szilagyi ◽  
C. M. Ferrario
Keyword(s):  
Angiotensin Ii ◽  
Vertebral Artery ◽  
Area Postrema ◽  
Pressor Response ◽  
Cardiovascular Effects ◽  
Endogenous Opiates ◽  
Pressor Responses ◽  
Vasomotor Activity ◽  
The Brain

1. Intra-vertebral artery-administered angiotensin II acts at the area postrema to facilitate central sympathetic vasomotor activity. Recent evidence suggests a possible role of the opiate system in the mechanism of action of angiotensin II at the level of the brain stem. 2. In these experiments, we show that the morphine antagonist naloxone reduces significantly the magnitude of the pressor response to vertebral artery-infused angiotensin II. 3. Morphine, in contrast, doubled the peak of the vertebral response to identical doses of the peptide. Neither naloxone nor morphine affected the pressor responses to intravenously administered angiotensin II. 4. The data suggest that the endogenous opiate system in the medulla modulates the cardiovascular effects of angiotensin II at the level of the area postrema.

scholarly journals Signal Transduction of Mineralocorticoid and Angiotensin II Receptors in the Central Control of Sodium Appetite: A Narrative Review

2021 ◽  
Vol 22 (21) ◽  
pp. 11735
Author(s):  
Michele Iovino ◽  
Tullio Messana ◽  
Giuseppe Lisco ◽  
Aldo Vanacore ◽  
Vito Angelo Giagulli ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Salt Intake ◽  
Sodium Intake ◽  
Zona Glomerulosa ◽  
Narrative Review ◽  
Mitogen Activated Protein Kinase ◽  
Central Control ◽  
Ang Ii ◽  
Sodium Appetite ◽  
Mesh Terms

Sodium appetite is an innate behavior occurring in response to sodium depletion that induces homeostatic responses such as the secretion of the mineralocorticoid hormone aldosterone from the zona glomerulosa of the adrenal cortex and the stimulation of the peptide hormone angiotensin II (ANG II). The synergistic action of these hormones signals to the brain the sodium appetite that represents the increased palatability for salt intake. This narrative review summarizes the main data dealing with the role of mineralocorticoid and ANG II receptors in the central control of sodium appetite. Appropriate keywords and MeSH terms were identified and searched in PubMed. References to original articles and reviews were examined, selected, and discussed. Several brain areas control sodium appetite, including the nucleus of the solitary tract, which contains aldosterone-sensitive HSD2 neurons, and the organum vasculosum lamina terminalis (OVLT) that contains ANG II-sensitive neurons. Furthermore, sodium appetite is under the control of signaling proteins such as mitogen-activated protein kinase (MAPK) and inositol 1,4,5-thriphosphate (IP3). ANG II stimulates salt intake via MAPK, while combined ANG II and aldosterone action induce sodium intake via the IP3 signaling pathway. Finally, aldosterone and ANG II stimulate OVLT neurons and suppress oxytocin secretion inhibiting the neuronal activity of the paraventricular nucleus, thus disinhibiting the OVLT activity to aldosterone and ANG II stimulation.

Glomerular angiotensin II receptor subtypes during development of rat kidney

1993 ◽  
Vol 265 (2) ◽  
pp. F264-F271 ◽  
Author(s):  
G. M. Ciuffo ◽  
M. Viswanathan ◽  
A. M. Seltzer ◽  
K. Tsutsumi ◽  
J. M. Saavedra
Keyword(s):  
Angiotensin Ii ◽  
Kidney Development ◽  
Developmental Stages ◽  
Rat Kidney ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Kidney Medulla ◽  
At1 Receptors ◽  
Old Rats

We used quantitative autoradiography to investigate distribution of angiotensin II (ANG II) receptor subtypes during development of the kidney in the rat. In fetal, newborn, and 3-day-old rats, immature glomeruli in the form of comma and S-shaped bodies, located in the nephrogenic zone of the renal cortex, expressed only the angiotensin AT2 receptor subtype. Conversely, the juxtamedullary glomeruli, in more advanced developmental stages, expressed only the AT1 subtype. Similarly, maturing and fully developed glomeruli, present in 1-, 2-, and 8-wk-old rats, expressed only AT1 receptors. In the kidney medulla, there was a similar change in ANG II receptor subtype expression, with the AT2 subtype expressed earlier and the AT1 subtype later during development. Our results demonstrate a selective expression of ANG II receptor subtypes during kidney development. We have found glomerular and medullary AT1 receptors only at developmental stages when kidney function has matured. Conversely, AT2 receptors are expressed only in immature structures, suggesting that they may have a role during kidney organogenesis.

Angiotensin II receptor isoforms in the rat adrenal gland: studies with the selective subtype antagonists DuP 753 and CGP42112A

1993 ◽  
Vol 11 (1) ◽  
pp. 69-75 ◽  
Author(s):  
M Montiel ◽  
S Barker ◽  
G P Vinson ◽  
E Jiménez
Keyword(s):  
Angiotensin Ii ◽  
Adrenal Gland ◽  
Binding Sites ◽  
Specific Binding ◽  
Zona Glomerulosa ◽  
Scatchard Analysis ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Receptor Isoforms

ABSTRACT The angiotensin II (Ang II)-binding sites in rat adrenal gland membranes were characterized using 125I-radiolabelled Ang II. While Scatchard analysis identified a single population of Ang II receptor sites, isoelectric focusing (IEF) on polyacrylamide gels revealed four peaks of specific Ang II binding which migrated to isoelectric points (pI values) 6·8, 6·7, 6·5 and 6·3. In binding assays in the presence of an excess of the Ang II receptor AT1 subtype antagonist DuP 753, a monophasic dose-dependent displacement of 125I-labelled Ang II binding by the Ang II receptor AT2 subtype antagonist CGP42112A was observed, and vice versa. In this system, reduction of disulphide bridges using 1 mmol dithiothreitol (DTT)/l markedly increased the number of binding sites in the adrenal zona glomerulosa without affecting receptor affinity. Using IEF, it was found that both DuP 753 and CGP42112A were able to reduce specific binding of each of the four peaks to some extent. However, the predominant effect of DuP 753 was to reduce the labelling of the isoform at pI 6·7 substantially, while CGP42112A significantly inhibited the specific 125I-labelled Ang II binding to the pI 6·3 isoform. When DuP 753 and CGP42112A were used together, specific binding of 125I-labelled Ang II to the isoforms of pI values 6·8, 6·7 and 6·3 was completely eliminated. These data suggest that the four peaks of specific binding found may be composed of different isoforms of both AT1 and AT2 receptor subtypes and that the Ang II receptor isoforms which migrated to pI 6·7 and pI 6·3 are predominantly composed of AT1 and AT2 receptor subtypes respectively. Interestingly, in the presence of both antagonists, 8·7 ± 0·9% of the specific binding migrating at pI 6·5 remained unaffected. This finding suggests the presence of an additional subtype, which is neither AT1 nor AT2, in the rat adrenal zona glomerulosa. In further studies, pretreatment with DTT was found to increase the specific 125I-labelled Ang II binding of all four isoforms. Moreover, DTT also produced a further specific binding component between pI 6·5 and pI 6·7 which exhibited AT2 subtype pharmacology in DTT-treated preparations. Since DTT has been reported to enhance only AT2 subtype binding this also suggests that the different isoforms may contain components related to both AT1 and AT2 receptor subtypes.

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