High impact information on Exp 655

• Oral treatment with PD 123177 (50 mg/liter drinking water) attenuated the glomerular M/M influx without normalizing the slightly elevated systolic blood pressure caused by ANG II infusion, suggesting that the effects on blood pressure and RANTES induction can be separated [1].
• However, after pretreatment of quiescent endothelial cells (< passage 4) with the AT2-receptor antagonist, PD 123177, ANG II induced proliferation [2].
• The AT1-receptor antagonist DUP 753 significantly reduced E-selectin-dependent adhesion, whereas the AT2-receptor antagonist PD 123177 had no inhibitory effect [3].
• About 85% of the binding sites of the glomerulosa zone and 30% of those of the inner zones were of the AT1 subtype, with relative affinities for the nonpeptide antagonists Dup 753 and PD 123177 and the peptide antagonist CGP 42112A in the order of Dup 753 much greater than CGP 42112A greater than PD 123177 [4].
• In these areas, binding was not affected by the selective AT2 competitors PD 123177 or CGP 42112 A, indicating the presence of AT1 and the absence of AT2 receptors [5].

Biological context of Exp 655

• In contrast, only AT2 receptor-specific antagonists were potent inhibitors of [3H]ARA release (CGP 42112A IC50 approximately 7 nM, EXP 3880 IC50 approximately 2 nM, and PD 123177 IC50 approximately 10 nM) [6].
• Angiotensin II evoked AP-A activity in first trimester trophoblast, and Losartan and PD 123177 in combination significantly inhibited this induction of AP-A activity [7].

Anatomical context of Exp 655

• The selective AT-2 displacers CGP 42112 A and/or PD 123177 competed with high affinity with AT bound to most receptors located in skeletal muscle, skin, diaphragm, bronchi, and stomach, and these receptors are classified as AT-2 receptors [8].
• The use of the specific Ang II antagonists CGP 42112A, PD 123177, and DuP 753 revealed that the pancreas expresses two receptor subtypes [9].
• In both the sinoatrial and atrioventricular nodes, binding could be totally displaced by losartan, and was insensitive to PD 123177, indicating that angiotensin II receptors in the conduction system of the rat heart belong to the AT1 subtype [10].
• Angiotensin-II (A-II) receptor subtypes and their potential coupling mechanisms were investigated in bovine adrenal fasciculata cells (BAC) in culture, by the use of selective antagonists for AT1 (DUP 753 or Losartan) and AT2 (PD 123177 and CGP 42112A) sites [11].

Associations of Exp 655 with other chemical compounds

• However, binding of 125I-labeled [Sar1,Ile8]AII in the latter regions was inhibited by the AT2 receptor antagonists PD 123177 and CGP 42112A [12].
• Both an initial (10 s) and secondary (10 min) phase of DAG production in response to 100 nM Ang II were inhibited by 1 microM losartan (DuP 753), an AT1 antagonist, while 1 microM PD 123177, an AT2 antagonist, was ineffective [13].
• Specific binding to angiotensin II receptors in heart grafts was displaced by addition of the AT1 receptor antagonist losartan, but not by addition of the AT2 receptor competitor PD 123177 [14].
• RG 13647 (1(-1,4-benzodioxan-2-methyl)-5-diphenylacetyl-4,5,6,7-tetra hydro-1H-imidazo- [4,5,c]-pyridine-6-carboxylic acid) represents a potent and AT2-selective analog of PD 123177 and showed weak activity in competing for [125I]angiotensin II binding with an IC50 value of 100 microM [15].
• In the present study we attempted to mimic the actions of PD-123319 by giving a supramaximal dose of EXP-3174 (10 micrograms), and we also assessed the effects of PD-123177 (80 micrograms), an AT2-receptor antagonist that differs from PD-123319 only by a dimethyl group [16].

Gene context of Exp 655

• Conversely, the AT2 receptor antagonist PD 123177 (1 mumol/L) was ineffective [17].
• RESULTS: All binding in the presence of DUP 753 and PD 123177 confirmed that nuclear All receptors can be classified as AT1 receptors and that as much as 10% of the specific binding is attributable to nuclear chromatin [18].
• The sites having high affinity for DuP 753 are designated as site 1 (AT1 receptors) and those having a high affinity for PD 123177 as site 2 (AT2 receptors) [19].
• In contrast, both CGP 42112A (10 and 100 microM, n = 12) and PD 123177 (100 microM, n = 7) failed to block excitation by Ang II in all neurons tested [20].
• Pretreatment of the PVN with losartan or the AT2 receptor antagonist, PD 123177 (4 nmol/200 nl), inhibited the 100 pmol ANG (1-7)-induced AVP release [21].

References