The genomic organization of the rat AT1 angiotensin receptor

Langford, Kimberly G.; Frenzel, Kristen; Martin, Brian M.; Bernstein, Kenneth E.

doi:10.1016/s0006-291x(05)80293-1

Cited by 55 publications

(19 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, differential regulation could be determined by the genomic structure of the receptor. Although the structure of the AT 1A receptor gene has recently been reported, 32 the genomic structure of the AT 1B receptor has not been determined. It will be important to study the differential regulation of these two distinct genes under conditions that alter the activity of the RAS.…”

Section: Discussionmentioning

confidence: 99%

Regulation of angiotensin II receptors in rat brain during dietary sodium changes.

Sandberg

Catt

1994

Hypertension

View full text Add to dashboard Cite

Activation of the renin-angiotensin system by sodium deficiency is associated with reciprocal changes in the expression of angiotensin II receptors in adrenal glomerulosa and vascular smooth muscle cells. The effects of dietary sodium changes on the expression of brain angiotensin receptor subtype 1 (AT,) mRNAs were examined in rats maintained on normal, low, and high sodium intake for 3 weeks. Plasma aldosterone and renin activity were elevated in rats maintained on a low salt diet compared with normal rats and were reduced in rats maintained on a high salt diet. These results are consistent with previous findings on the effects of altered dietary sodium on the renin-angiotensin system. The expression of AT 1A and AT 1B receptor subtype mRNAs was determined by quantitative reverse transcriptase-polymerase chain reaction during changes in sodium intake. The results revealed that sodium deprivation enhanced the expression of AT 1B receptors in decorticated brains by 164% compared with high sodium intake. Conversely, high sodium diet increased the expression of AT 1A receptors by 155% in the brain compared with low sodium intake. These data suggest that AT 1A and AT 1B receptors play reciprocal roles in central mechanisms for the control of fluid homeostasis. Further analysis of the molecular biology of angiotensin II receptor regulation in the brain may provide new insights into the interplay between the renin-angiotensin system and blood pressure regulation and also into the role of angiotensin II in the pathogenesis of essential hypertension. The octapeptide hormone angiotensin II (Ang II) is one of the major regulators of electrolyte balance and cardiovascular function and is one of the most potent circulating vasoconstrictor hormones. Ang II modulates peripheral vascular tone, enhances salt retention (via aldosterone release), and exerts central pressor and dipsogenic effects. It also has been postulated that abnormalities in the RAS could contribute to congestive heart failure, peripheral vascular disease, and essential hypertension. -3The cardiovascular neuronal centers within the brain are considered to mediate Ang II actions, including pressor, tachycardiac, and dipsogenic responses. -5 Several lines of evidence indicate that the RAS operates in the brain as a long-term regulator of arterial pressure and sodium balance and is involved in the pathogenesis of hypertension. In the renal hypertensive dog, elevated levels of Ang II were found in the cerebrospinal fluid and were not altered by nephrectomy.6 Ang II antagonists or angiotensin converting enzyme inhibitors normalized blood pressure in hypertensive rats, 7 and lesions in brain regions possessing Ang II receptors attenuated experimental hypertension.8 Furthermore, Ang II receptors were found to be associated with various cardiovascular regulatory sites in the brain. 910These receptor sites are mainly located in the circumventricular organs, where they can detect blood and/or cerebrospinal fluid levels of Ang II.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of angiotensin II receptors in rat brain during dietary sodium changes.

Sandberg

Catt

1994

Hypertension

View full text Add to dashboard Cite

show abstract

“…A computer-assisted search was done on the 5'-flanking sequence of the rat ATIA (42,43), rat AT1B (44), and human AT1 (45) genes to look for exact matches with well-defined transcriptional control elements. Sites for interaction with the RNA polymerase II transcriptional complex including TATA box and GC box were found proximally upstream from the transcriptional start site, and some regulatory elements were also found in the 5'-flanking regions (Fig.…”

Section: Regulation Of Gene Expressionmentioning

confidence: 99%

Angiotensin II Receptor: Molecular Cloning, Functions, and Regulation.

Inagami

Kitami

1994

Hypertens Res

View full text Add to dashboard Cite

Angiotensin II receptors are diverse and mediate complex signaling mechanisms.Their isoforms AT1 and AT2 have been cloned. AT1 consists of two closely related subtypes, AT1A and AT1B, in rodents. AT1A is expressed preferentially in the kidney, liver and cardiovascular tissues, whereas, ATIB is found mainly in endocrine tissues like the adrenal and pituitary glands. In higher mammals only a single isoform of AT1 has been reported.AT1 accounts for the majority of actions traditionally ascribed to angiotensin II that include the Gq-protein coupled activation of phospholipase C, Gi-coupled opening of an L-type calcium channel. AT2 was cloned recently from rat tissues and cell lines. It has a structure compatible with a seven transmembrane domain receptor in spite of the lack of internalization or shift to the low affinity state by stable GTP analogs. AT2 was found to inhibit certain phosphotyrosine phosphatase(s) by a pertussis toxin-sensitive mechanism. These cloned cDNAs and their mutated cDNAs have been expressed in mammalian cells to identify various functional domains such as ligand binding sites, domains for interaction with various G-proteins, and for desensitization. Both AT1 and AT2 genes consist of 3-5 exons. Their coding regions are contained in a single exon. Angiotensin II down-regulates the expression of the AT1 gene by two different mechanisms, whereas, glucocorticoids up-regulates it. (Hypertens Res 1994; 17: 87-97)

show abstract

“…25,26 The rat AT 1A R (rAT 1A R) gene is composed of 3 exons and spans Ͼ40 kb ( Figure 1). [27][28][29] Exons 1 and 2 constitute the 5Ј-untranslated region (UTR) sequence, whereas exon 3 harbors the uninterrupted open reading frame (ORF) for the rAT 1A R and the entire 3Ј-UTR, which contains 2 polyadenylation sequences. Primer extension and S1 mapping identified a single transcription initiation site 31 bp downstream of a TATA sequence.…”

Section: At 1 R Gene Structurementioning

confidence: 99%

Angiotensin II Type 1 Receptor Gene Regulation

Elton

Martin

2007

Hypertension

View full text Add to dashboard Cite

A ngiotensin II (Ang II), the major bioactive peptide of the renin-angiotensin system, was originally described as a potent vasoconstrictor. It is now recognized as a multifunctional hormone influencing many cellular processes, including cell growth, apoptosis, migration, inflammation, and fibrosis. 1,2 Under pathological conditions, the vasoconstrictor, mitogenic, proinflammatory, and profibrotic actions of Ang II contribute to altered vascular tone, structural remodeling, and endothelial dysfunction. [3][4][5][6] Thus, Ang II plays a key role in the pathogenesis of cardiovascular diseases.The biological responses of Ang II are mediated by its interaction with 2 distinct high-affinity G protein-coupled receptors now designated Ang II type 1 receptor (AT 1 R) and Ang II type 2 receptor. 7 Most of the known physiological and pathophysiological effects of Ang II are mediated via the AT 1 R. [1][2][3][4][5][6][7] This receptor subtype is expressed in cardiovascular-relevant cell types including vascular smooth muscle cells (VSMCs), endothelial cells, cardiac myocytes, cardiac fibroblasts, and renal mesangial cells. 7 The multiple actions of Ang II, mediated through the AT 1 R, are a result of complex intracellular signaling pathways including stimulation of the phospholipase C/inositol 1,4,5-trisphosphate/diacylglycerol cascade, mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases, tyrosine kinases, and RhoA/Rho kinase. 1,2,4,6,7 In addition, AT 1 Rs mediate many of their pathophysiological effects by stimulating reactive oxygen species generation via an reduced nicotinamide-adenine dinucleotide/reduced nicotinamide-adenine dinucleotide phosphate oxidase-dependent mechanism. 2,8 Reactive oxygen species, in turn, influences downstream signaling molecules, including transcription factors, tyrosine kinases/phosphatases, Ca 2ϩ channels, and MAPKs. 2,8 The expression level of the AT 1 R defines the biological efficacy of Ang II; hence, overexpression of the AT 1 R is one potential mechanism by which Ang II can contribute to cardiovascular disease. Importantly, aberrant expression of the AT 1 R has been shown to have pathophysiological relevance in cell culture, animal studies, and in clinical interventional trails (reviewed in Reference 5). This review will summarize the transcriptional and posttranscriptional mechanisms by which AT 1 R gene expression is regulated and discuss the pathological relevance of these mechanisms in mediating cardiovascular disease. AT 1 R Gene StructureTo initiate the investigations into the mechanisms by which AT 1 R expression is regulated, the AT 1 R gene has been cloned from a variety of species. Uniquely, the rodent genome harbors 2 distinct AT 1 R genes: AT 1A R and AT 1B R. 9 -15 The AT 1A R gene has been localized to chromosomes 17 and 13 of the rat and mouse, respectively, whereas the AT 1B R gene has been localized to chromosomes 2 and 3 of the rat and mouse, respectively. 14,15 It has been suggested that both receptor subtypes are pharmacologically and fu...

show abstract

The genomic organization of the rat AT1 angiotensin receptor

Cited by 55 publications

References 6 publications

Regulation of angiotensin II receptors in rat brain during dietary sodium changes.

Regulation of angiotensin II receptors in rat brain during dietary sodium changes.

Angiotensin II Receptor: Molecular Cloning, Functions, and Regulation.

Angiotensin II Type 1 Receptor Gene Regulation

Contact Info

Product

Resources

About