Disease relevance of Agtr1b

• On the other hand, the AT1A and AT1B receptor mRNA levels were not altered in the cortex or hippocampus during the early reperfusion period, even 3 h and 24 h after ischemia [1].
• Our results show that prolonged water deprivation selectively regulates AT1 receptor expression and AT1A and AT1B receptor mRNA levels in the subfornical organ and anterior pituitary, respectively, supporting a role for these receptors during sustained dehydration [2].
• METHODS: The expression of angiotensin II receptor subtype (AT1A and AT1B) mRNAs was studied by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in the four zones of the kidneys of Sabra rats, sensitive or resistant to DOCA salt-induced hypertension (SBH/y and SBN/y, respectively) [3].
• The mechanism of the regression appears to be dual: inhibition of collagen synthesis due to AT1 receptor antagonism and activation of metalloproteinases that is probably associated with the degree of fibrosis independently of AT1 blockade [4].
• While lung and lymph-node metastases developed in host animals inoculated with parental AT3 and MAT-LyLu cells, no metastases developed in the multidrug-resistant progeny of these cell lines [5].

Psychiatry related information on Agtr1b

• AT1B mRNA was predominant in subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), the two regions that mediate angiotensin II-induced drinking behavior, and also in cerebellum [6].

High impact information on Agtr1b

• In rodents, two AT1 receptor subtypes, AT1A and AT1B, have been isolated [7].
• Agonist-induced endocytosis and processing of the G protein-coupled AT1 angiotensin II (Ang II) receptor (AT1R) was studied in HEK 293 cells expressing green fluorescent protein (GFP)- or hemagglutinin epitope-tagged forms of the receptor [8].
• METHODS AND RESULTS: In separate studies, three Ang II receptor antagonists, including AT1 selective (L-158,809), balanced AT1/AT2 (L-163,082), and AT2 selective (L-164,282) agents, were evaluated for their ability to inhibit vascular intimal thickening in a porcine coronary artery model of vascular injury [9].
• CONCLUSIONS: These findings indicate that chronic blockade of Ang II receptors by either site-selective or balanced AT1/AT2 antagonists is insufficient to inhibit intimal hyperplasia after experimental coronary vascular injury in the pig [9].
• The change in PKC epsilon distribution and in TnI phosphorylation in diabetic animals was completely prevented by rendering the animals euglycemic with insulin or by concomitant treatment with a specific angiotensin II type-1 receptor (AT1) antagonist [10].

Chemical compound and disease context of Agtr1b

• We studied angiotensin II (ANG II) receptor subtype expression in selected brain nuclei and pituitary gland after water deprivation by in vitro receptor autoradiography using 125I-labeled [Sar1]ANG II and by in situ hybridization using 35S-labeled AT1A, AT1B, and AT2 receptor-specific riboprobes [2].
• DESIGN: TGR(mREN2)27 were treated orally with the newly developed AT1-specific angiotensin receptor antagonist Telmisartan, 4'-[(1,4'-dimethyl-2'-propyl[2,6'-bi-1H-benzimidazol]-1'-yl) methyl]-[1,1'-biphenyl]-2-carboxylic acid, in three doses (0.1, 1 and 3 mg/kg body weight) for 9 weeks [11].
• Role of AT1 receptors and NAD(P)H oxidase in diabetes-aggravated ischemic brain injury [12].
• 1. The present studies were designed to measure the affinity of UP 269-6, a newly developed angiotensin AT1 receptor antagonist, for vascular AT1 receptors from normotensive and hypertensive rats and to investigate in vitro, its effects on angiotensin II (AII)-induced hyperplasia and hypertrophy of vascular smooth muscle cells (VSMC) [13].
• Hypertension and losartan did not change AT1B mRNA expression [14].

Biological context of Agtr1b

• Gene expressions of AT1A and AT1B receptors were not significantly altered in either strain during the time in culture [15].
• This downregulation was specific for the AT1A subtype since the renal expression of the AT1B subtype remained normal in hypertensive rats [16].
• This study presents a new approach for the specific quantification of AT1A and AT1B receptor mRNAs by reverse transcription and polymerase chain reaction amplification in the presence of an AT1 receptor mutant cRNA as internal standard [17].
• The selective AT2 receptor ligand, CGP 42112A, antagonized AII-induced [3H]-thymidine incorporation with an IC50 of 6.3 +/- 1.3 microM while the AT2/AT1B receptor antagonist, PD 123319, was found to be almost inactive (IC50 > 10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)[18]
• The AT1C receptor nucleotide sequence homology was greatest to the described AT3 receptor (95%) and less so to the published AT1A (90%) and AT1B (82%) receptor subtypes [19].

Anatomical context of Agtr1b

• Analysis of RNA expression by RT-PCR showed the presence of both subtypes, AT1A and AT1B in endothelial cells, whereas smooth muscle cells express only AT1A [20].
• Our results show that AT1A and AT2 mRNAs are expressed in rat choroid, iris/ciliary body and retinas, whereas AT1B mRNA is not expressed in the retina but in all other ocular tissues under investigation [21].
• In rat mesangial cells two subtypes of AT1 receptor could be distinguished, AT1A subtype is more sensitive to losartan whereas AT1B subtype is more sensitive to PD123319, but insensitive to CGP42112A [22].
• In contrast, using in situ hybridization histochemistry we found only AT1A and AT1B but not AT2 receptor mRNA in the cerebellar cortex of young rats [23].
• The half lives of AT1 receptors are highly variable, ranging from 36 days in the anterior pituitary to 442 days in the nucleus of the solitary tract, and this might be related to variable stability of AT1A and AT1B receptors [24].

Associations of Agtr1b with chemical compounds

• Using fluorescence in situ hybridization, we determined the regional localization of the 3 rat genes encoding angiotensin II receptors at 17q12 (Agtr1a), 2q24 (Agtr1b) and Xq34 (Agtr2) [25].
• Adrenal mRNA levels for AT2 (P< 0.001) and AT1A (P< 0.01), but not AT1B (P>0.05), were increased in guanethidine-treated rats compared with vehicle (P< 0.01) [26].
• The stimulatory effect of AII (3 nM) on [3H]-thymidine incorporation in VSMC was antagonized by the non-selective AT1/AT2 receptor antagonist, [Sar1, Ile8]-AII (IC50 = 5.6 nM), by the AT1A/AT1B receptor antagonist, losartan (IC50 = 10.5 nM) and the AT1 receptor antagonist, L-158809 (IC50 = 0.20 nM) [18].
• TCV-116 did not affect the levels of expression of AT1A and AT1B receptor mRNAs in the adrenal gland [27].
• Thus, AT1A receptors in the dorsal arcuate nucleus and AT1B receptors in the anterior pituitary are regulated inversely by estrogen/progesterone treatment, supporting the hypothesis of a dual role for brain and pituitary Ang II on prolactin release [28].

Regulatory relationships of Agtr1b

• AT1A subtype mRNA was expressed in vascular smooth muscle whereas AT1B mRNA was expressed in adrenal and pituitary [6].
• In the present study we used the Ang II subtype 1 (AT1) receptor antagonist losartan to investigate whether rising plasma Ang II levels stimulate angiotensinogen production to counteract the falling plasma angiotensinogen levels caused by increasing renin activity in plasma [29].
• This effect was transduced by angiotensin receptor type-1 (AT1) and was inhibited by a flavoprotein inhibitor (DIP) or p22phox antisense oligonucleotides, indicating the involvement of membrane NAD(P)H oxidase [30].

Other interactions of Agtr1b

• These findings are consistent with AngII mediated signal transduction through AT1A and AT1B sites for phospholipase C mediated [Ca(2+)]i mobilization and inhibition of adenylyl cyclase [22].
• Moreover, differences in Agtr1b mRNA abundance and sequence reinforce the putative role of the Agtr1b gene in the differential plasma renin stress reactivity between the two rat strains [31].
• In conclusion, glucocorticoids diminish Ang II receptor density at the mesangial cell surface through a mechanism that implies successive interaction with the glucocorticoid receptor and specific reduction in AT1B receptor mRNA expression [32].
• METHODS AND RESULTS: Oral administration of either the endothelin A (ETA) and ETB receptor antagonist bosentan or the angiotensin type 1 (AT1) receptor antagonist valsartan for 12 weeks reduced systolic blood pressure (SBP) of nondiabetic and diabetic Ren-2 rats to normotensive levels [33].
• These findings indicate that stretch-stimulated DNA synthesis and gene expression in normal bladder SMC occur via multiple independent receptor systems (e.g., AT1 and ErbB2) and at least one MAPK pathway (p38 SAPK2) [34].

Analytical, diagnostic and therapeutic context of Agtr1b

• Sequence analysis indicated, however, that the cDNA fragment was a mixture of two highly similar gene products: the first cDNA was identical to the previously cloned AT1 receptor (termed here AT1A) whereas the second cDNA (termed here AT1B) was 92% identical at the nucleotide level and 96% identical at the amino acid level [35].
• We report that [125I]Sar1-Ang II binding to AT1 receptors and AT1A receptor mRNA expression increase selectively in the dorsomedial arcuate nucleus of 17beta-estradiol-primed ovariectomized rats after treatment with progesterone [28].
• In the adrenal gland, in which the AT1B receptor is predominant, low salt diet led to a transient increase in the expression of this receptor gene, with a maximum around day 10 of feeding [36].
• Both reverse transcription-polymerase chain reaction and Northern blot analysis using specific short probes from the 3' noncoding region of the cDNA demonstrated the presence of AT1A and AT1B receptor mRNAs in rat mesangial cells, with a slight predominance of AT1B [32].
• Structural assessment of the expressed AT1 receptors by two-dimensional Western blotting revealed that a spectrum of structurally distinct AT1 receptor isoforms is expressed in the renal tissues of both animal models [37].

References