Disease relevance of AGTR2

• Neither AGTR1 nor AGTR2 polymorphisms were associated with sarcoidosis [1].
• The patients with AGTR2 sequence variants had severe/profound mental retardation, epileptic seizures, restlessness, hyperactivity, and disturbed development of speech [2].
• AGTR2 mutations in X-linked mental retardation [3].
• Haplotypes of the angiotensin II receptor genes AGTR1 and AGTR2 in women with normotensive pregnancy and women with preeclampsia [4].
• Changes of AT2 Bmax in uterine leiomyomas during pregnancy or with oral contraceptive were similar to those in the myometrium [5].

Psychiatry related information on AGTR2

• Identification of two AGTR2 mutations in male patients with non-syndromic mental retardation [2].
• In addition, the marked increase in the levels of angiotensin AT2 receptor recognition sites in temporal cortex from patients with Alzheimer's disease correlates with some other markers associated with the renin-angiotensin system previously investigated in tissue from patients with this neurological disease [6].
• In brain tissue homogenates from patients with Huntington's disease, the angiotensin AT1 receptor recognition site levels were decreased by approximately 30% in putamen relative to the control patients whilst angiotensin AT2 receptor levels were increased by some 90% in the caudate nucleus relative to the control patients [6].
• Déjà vu, a warm sensation, an indescribable strange sensation, a cephalic sensation, and fear were associated with an abnormal AT2 [7].

High impact information on AGTR2

• AT1 receptors mediate most known functions of angiotensin II, while AT2 receptors may be important developmentally [8].
• AGTR2, therefore, has a significant ontogenic role for the kidney and urinary tract system [9].
• Studies of the human type 2 receptor (AGTR2) gene in two independent cohorts found that a significant association exists between CAKUT and a nucleotide transition within the lariat branchpoint motif of intron 1, which perturbs AGTR2 mRNA splicing efficiency [9].
• Quantitative receptor autoradiography using the nonselective radioligand [125I]ANG II and subtype-selective competing compounds demonstrated the presence of both ANG II receptor (AT)1 and AT2 receptor recognition sites [10].
• These observations also suggest, for the first time, the existence of a cross-talk between AT1 or AT2 receptors in trophoblast and that the reduction in placental AT1 receptors in IUGR may, in part, account for poor placental function in this disorder [10].

Chemical compound and disease context of AGTR2

• To explore the roles and regulation of the AT2 receptor in human uterus and to examine whether its expression is related to the proliferative characteristics of leiomyoma, we studied Ang II receptor gene expressions in nonpregnant and pregnant myometrium and in uterine leiomyomas obtained from patients who underwent gynecological surgery [5].
• Angiotensin II regulates phosphoinositide 3 kinase/Akt cascade via a negative crosstalk between AT1 and AT2 receptors in skin fibroblasts of human hypertrophic scars [11].
• Male rat pituitary glands, diethylstilbestrol (DES)-induced rat pituitary tumors and 12 human pituitary adenomas were immunostained with antibodies raised against AT1 and AT2 angiotensin receptor proteins [12].
• (1992) reported increased AT2 receptor expression following neuroblastoma differentiation with dibutyryl cyclic AMP and DMSO/low serum, respectively, and suggested a role for the AT2 receptor in neuronal differentiation [13].
• AT1 receptor blockade and increased AT2 receptor stimulation after administration of candesartan may contribute to the protection against brain ischemia and inflammation [14].

Biological context of AGTR2

• ARB significantly lowered IOP in normal subjects, but the male subjects with the AGTR2/3123A genotype had significantly less lowering of IOP than those with the C genotype (P = 0.014) [15].
• RESULTS: There was no difference in allele frequency of AGTR1 and AGTR2 polymorphism among the three groups [1].
• Although no significant difference was seen in the clinical characteristics of female patients with NTG who carried the AGTR2/3123C-->A genotype, patients with CC in the AGTR2 gene had significantly worse visual field scores if they carried ACE/ID+DD (i.e., D carriers; P = 0.012) [15].
• Assignment of the human angiotensin II type 2 receptor gene (AGTR2) to chromosome Xq22-q23 by fluorescence in situ hybridization [16].
• A total of 107 families (father, mother, and baby) with FGR, and 101 families with normal pregnancies were genotyped at five sites in AGTR1 and six sites across AGTR2 [17].

Anatomical context of AGTR2

• These results indicate that human myometrium contains almost exclusively the AT2 receptor subtype [18].
• Association and dissociation studies performed with 125I-AII on human myometrium membranes revealed that AII had a very high affinity for AT2 receptors, with a Kd of 0.01 nM (association rate constant K1 = 1.056 x 10(12) mol-1 min-1; dissociation rate constant K2 = 0.003 min-1) [18].
• The uterus expresses the AT2 receptor abundantly even in adults, suggesting its role in reproduction [5].
• In their amino-terminal portion, ATIP polypeptides exhibit distinct motifs for localisation in the cytosol, nucleus or cell membrane, suggesting that MTUS1 gene products may be involved in a variety of intracellular functions in an AT2-dependent and independent manner [19].
• All components could additionally be demonstrated at mRNA level in cultured primary keratinocytes, melanocytes, dermal fibroblasts and dermal microvascular endothelial cells, except for AT2 receptors in melanocytes [20].

Associations of AGTR2 with chemical compounds

• Two angiotensin II (Ang II)-specific receptors, AGTR1 and AGTR2, are expressed in the mammalian brain [3].
• There are very few data regarding the regulation of the subtype AT2, indicating modulation by a number of growth factors and by Ang II [21].
• In nonpregnant myometrium (n = 5), receptor density [maximum binding capacity (Bmax)] and dissociation constant (Kd) for AT2-selective CGP42112A were 287 +/- 46 fmol/mg protein and 0.48 +/- 0.09 nM, respectively [5].
• Autoradiography of the polyacrylamide gel revealed a single band, of 68 kDa, and the labeling of this band was completely abolished in the presence of 1 microM PD 123319, indicating selective labeling of the AT2 receptor subtype [18].
• [125I]-Ang IV binding was not modified by nonpeptide AT1 (losartan) or AT2 (PD123177) antagonists [22].

Physical interactions of AGTR2

• We report here that MTUS1 encodes a family of proteins whose leader member (ATIP1) was previously isolated in our laboratory as a novel interacting partner of the angiotensin II AT2 receptor involved in growth inhibition (Nouet, JBC 279: 28989-97, 2004) [19].
• AT1 and AT2 receptor binding were determined with the AT1 receptor antagonist losartan [23].

Regulatory relationships of AGTR2

• The inhibitory effect of Ang II on VEGF-induced migration of endothelial cells was mimicked by the specific AT2 receptor agonist CGP-42112A [24].
• Recent evidence suggests that angiotensin II (Ang II) may promote growth through the AT1 and inhibit growth through the AT2 receptor subtypes [25].
• Both the AT1 and AT2 ligands administered into the LPO elicited a decrease in the NaCl intake induced by AVP injected into the LPO [26].
• In the gastrointestinal tract, physiological quantities of ANG II stimulate the AT2 receptor releasing NO and cGMP leading to increased sodium and water absorption [27].
• Furthermore, 10 of 23 (44%) patients with VUR and seven of 19 (42%) controls carried the AT2 receptor gene variation [28].

Other interactions of AGTR2

• CONCLUSION: Ang II decreases the activity of 11beta-HSD2 by an AT2 receptor- and MAPK-dependent mechanism [29].
• METHODS: We investigated the impact of the ACE, AGT, AT1, and AT2 genotypes on renal allograft function in 148 patients (77 men, 71 women) who underwent transplantation over a 5-year period [30].
• These constructs were transfected into human (HT1080) and rat (PC12W) cell lines and rat vascular smooth muscle cells, and luciferase activities were assessed, as well as the splice patterns of the chimeric AT2/luciferase mRNAs [31].
• In conclusion, this study indicates that AT2 receptor stimulation inhibits VEGF-induced endothelial cell migration and tube formation via activation of a PTX-sensitive G protein [24].
• Because some of these genes could be linked to the regulation of extracellular matrix association, we studied the effect of the AT2 receptor on cell migration [32].

Analytical, diagnostic and therapeutic context of AGTR2

• METHODS: ACE (I/D), angiotensin II type 1 receptor (AGTR1), and angiotensin II type 2 receptor (AGTR2) gene polymorphisms were investigated by polymerase chain reaction (PCR) and SACE levels were measured in three groups of patients: those with sarcoidosis or tuberculosis and normal controls [1].
• Northern blots revealed AT1 and AT2 receptor messenger RNA (mRNA) expressions in all samples examined; the former was much lower than the latter [5].
• We first analyzed the AT2 mRNA splice pattern by RT-PCR in myocardial samples from 12 explanted human hearts and compared it with the respective genotypes [31].
• Immunofluorescence studies demonstrated that stimulation with Ang II or CGP 42112 (an agonist of the AT2 receptor) strongly modified the actin network, now localized exclusively along the plasma membrane, with a predominance of labeling at the base of the bleb formation [33].
• Single copies of two distinct acetyltransferase genes, designated AT1 and AT2, were detected in hamster DNA by Southern blot analysis using gene-specific hybridization probes for the 3' end of the AT coding regions [34].

References