Increased Angiotensin II and Sustained Angiotensin II Receptor Expression in Nuclear and Plasma Membrane Compartments in the Kidney of the mRen2.Lewis Rat

Phospholipase D (PLD) is a key facilitator of multiple types of membrane vesicle trafficking events. Two PLD isoforms, PLD1 and PLD2, exist in mammals. Initial studies based on overexpression studies suggested that in resting cells, human PLD1 localized primarily to the Golgi and perinuclear vesicles in multiple cell types. In contrast, overexpressed mouse PLD2 was observed to localize primarily to the plasma membrane, although internalization on membrane vesicles was observed subsequent to serum stimulation. A recent report has suggested that the assignment of PLD2 to the plasma membrane is in error, because the endogenous isoform in rat secretory cells was imaged and found to be present primarily in the Golgi apparatus. We have reexamined this issue by using a monoclonal antibody specific for mouse PLD2, and find, as reported initially using overexpression studies, that endogenous mouse PLD2 is detected most readily at the plasma membrane in multiple cell types. In addition, we report that mouse, rat, and human PLD2 when overexpressed all similarly localize to the plasma membrane in cell lines from all three species. Finally, studies conducted using overexpression of wild-type active or dominant-negative isoforms of PLD2 and RNA interference-mediated targeting of PLD2 suggest that PLD2 functions at the plasma membrane to facilitate endocytosis of the angiotensin II type 1 receptor.

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Internalisation of the type I angiotensin II receptor (ATI) and angiotensin II function in the rat adrenal zona glomerulosa cell.

Journal of Endocrinology ◽

10.1677/joe.0.141r005 ◽

1994 ◽

Vol 141 (2) ◽

pp. R5-R9 ◽

Cited By ~ 10

Author(s):

G. P. Vinson ◽

M. M. Ho. ◽

J.R. Puddefoot ◽

R. Teja ◽

S. Barker

Keyword(s):

Monoclonal Antibody ◽

Plasma Membrane ◽

Angiotensin Ii ◽

Zona Glomerulosa ◽

Type I ◽

Specific Monoclonal Antibody ◽

Angiotensin Ii Receptor ◽

Cellular Localisation ◽

Glomerulosa Cells

ABSTRACT Little is known about the cellular localisation of the angiotensin II (AII) type 1 receptor (ATI) in the rat adrenal glomerulosa cell, but some studies have suggested that receptor internalisation and recycling may occur. Using a specific monoclonal antibody (6313/G2) to the first extracellular domain, we show here that most of the receptor is internalised in the unstimulated cell. When viable glomerulosa cells are incubated with 6313/G2, the receptor is transiently concentrated on the cell surface, and aldosterone output is stimulated. This stimulated output is enhanced by neither threshold nor maximal stimulatory concentrations of All amide, although the antibody does not inhibit All binding to the receptor. Conversely, the stimulatory actions of the antibody and those of ACTH are additive. The data suggest that recycling to the plasma membrane is constitutive, or regulated by unknown factors. Retention of the ATI receptor in the membrane is alone enough to allow sufficient G protein interaction to generate maximal stimulatory events.

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Meconium Increases Type 1 Angiotensin II Receptor Expression and Alveolar Cell Death

Pediatric Research ◽

10.1203/pdr.0b013e318163a2b8 ◽

2008 ◽

Vol 63 (3) ◽

pp. 251-256 ◽

Cited By ~ 13

Author(s):

Charles R Rosenfeld ◽

Alexander M Zagariya ◽

Xiao-Tie Liu ◽

Brigham C Willis ◽

Steven Fluharty ◽

...

Keyword(s):

Cell Death ◽

Angiotensin Ii ◽

Receptor Expression ◽

Angiotensin Ii Receptor ◽

Alveolar Cell

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Angiotensin II receptor blockade inhibits acute glomerular injuries with the alteration of receptor expression

Laboratory Investigation ◽

10.1038/labinvest.2008.128 ◽

2009 ◽

Vol 89 (2) ◽

pp. 164-177 ◽

Cited By ~ 17

Author(s):

Akiko Mii ◽

Akira Shimizu ◽

Yukinari Masuda ◽

Masamichi Ishizaki ◽

Hiroshi Kawachi ◽

...

Keyword(s):

Angiotensin Ii ◽

Receptor Expression ◽

Receptor Blockade ◽

Angiotensin Ii Receptor ◽

Angiotensin Ii Receptor Blockade

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GW26-e3962 Activation of D4 Dopamine Receptor Decreases AT1 Angiotensin II Receptor Expression in Rat Renal Proximal Tubule Cells

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2015.06.080 ◽

2015 ◽

Vol 66 (16) ◽

pp. C15-C16

Author(s):

Chen Ken ◽

Zeng Chunyu

Keyword(s):

Angiotensin Ii ◽

Proximal Tubule ◽

Dopamine Receptor ◽

Renal Proximal Tubule ◽

Receptor Expression ◽

Angiotensin Ii Receptor ◽

Proximal Tubule Cells ◽

Rat Renal Proximal Tubule ◽

Tubule Cells ◽

Renal Proximal Tubule Cells

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Difference in the Expression of Hormone Receptors and Fibrotic Markers in the Human Peritoneum—Implications for Therapeutic Targets to Prevent Encapsulating Peritoneal Sclerosis

Peritoneal Dialysis International ◽

10.3747/pdi.2010.00118 ◽

2011 ◽

Vol 31 (3) ◽

pp. 291-300 ◽

Cited By ~ 17

Author(s):

Niko Braun ◽

Peter Fritz ◽

Dagmar Biegger ◽

Martin Kimmel ◽

Fabian Reimold ◽

...

Keyword(s):

Vitamin D ◽

Angiotensin Ii ◽

Nuclear Receptors ◽

Hormone Receptors ◽

Transforming Growth Factor ◽

Angiotensin Converting Enzyme Inhibitors ◽

Receptor Expression ◽

Angiotensin Ii Receptor ◽

Converting Enzyme Inhibitors ◽

Significant Difference

ObjectiveEncapsulating peritoneal sclerosis (EPS) is a rare but life-threatening complication of peritoneal dialysis (PD). The optimal management of patients with EPS is uncertain. In the present study, we investigated differences in the expression of nuclear receptors [progesterone (PR), androgen (AR), vitamin D (VDR), and glucocorticoid (GCR)] in the human peritoneum. We also investigated estrogen receptor (ER), matrix metalloproteinase 9 (MMP9), and transforming growth factor β1 (TGFβ1) in the context of their potential role in tamoxifen therapy.MethodsWe analyzed clinical and histologic characteristics of 72 peritoneal biopsy specimens (22 from EPS patients, 11 from PD patients, 15 from uremic patients, and 24 from control subjects undergoing hernia repair). For immunophenotyping, we used antibodies against VDR, GCR, ER, PR, AR, MMP9, and TGFβ1.ResultsIn human peritoneum, VDR and GCR are highly expressed (98.6% and 87.3% respectively). Except in the case of VDR ( p = 0.0012), we observed no significant difference in receptor expression between the groups. Expression of ER and PR was sparse (11.4% and 31% respectively), with higher expression in women, and AR was absent. Minimal MMP9 expression and moderate TGFβ1 expression were observed in all groups. The differences between the groups were nonsignificant.ConclusionsNuclear receptors are present in human peritoneum. Except in the case of VDR, the pattern for any one group is nonspecific. Glucocorticoids, vitamin D, and angiotensin converting-enzyme inhibitors or angiotensin II receptor blockers (via the vitamin D/angiotensin II pathway) might be suitable interventions for preservation of the integrity of the peritoneal membrane. The mechanism of action of tamoxifen is still not elucidated, ER expression in the peritoneum is sparse, and data about the studied pathways (MMP9, TGFβ) are inconsistent.

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