Disease relevance of AGTR1

• In the present work we have investigated the effects of several growth factors on the expression of Angiotensin II (A-II) receptors subtype AT1 and their pertussis toxin-insensitive coupling to G-proteins in bovine adrenal fasciculata-reticularis cells (BAC) [1].

High impact information on AGTR1

• The effect of Ang IV (10 nM) was not inhibited by Dup 753 (1.0 microM), a highly specific antagonist of the AT1 receptor, or by PD123177 (1.0 microM), a highly specific antagonist of the AT2 receptor [2].
• AngII-mediated inhibition of bTREK-1 through the novel Ca2+-dependent pathway was blocked by the AT1 receptor antagonist losartan, or by including guanosine-5'-O-(2-thiodiphosphate) in the pipette solution [3].
• This effect of the hormone was completely prevented by losartan, a specific antagonist of the AT1 receptor subtype [4].
• This effect was abolished by losartan, a specific antagonist of the angiotensin II AT1 receptor [5].
• These findings indicate that AII-stimulated effects on IAC current, membrane voltage, and cortisol secretion are linked through a common AT1 receptor [6].

Chemical compound and disease context of AGTR1

• The coupling of AT1 to phosphoinositide breakdown is mainly pertussis toxin-insensitive suggesting that this receptor is coupled to Gaeq/Gae11 [7].
• The mitogenic effect of ANG II was not inhibited by pretreatment with pertussis toxin and was mediated by AT1 receptors as indicated by its sensitivity to the subtype-selective antagonist DuP-753 [8].

Biological context of AGTR1

• The adrenal glomerulosa cell is a major site of action of angiotensin II (AII), which binds to AT1 receptors to stimulate phosphoinositide hydrolysis and Ca2+ mobilization, and the subsequent production of aldosterone [9].
• The angiotensin AT1 and AT2 receptor subtypes have been linked with stimulated secretion of aldosterone and endogenous ouabain, respectively, but the second messenger mechanisms involved in the latter secretion are not known [10].
• In contrast, Transforming growth factor beta 1, which reduced slightly AT1 binding sites, but not the level of alpha q or alpha 11 proteins, did not change the A-II-induced inositol phosphate accumulation [1].
• Taken together, these results are interpreted as a down-regulation of the AT1 receptor [11].
• In BAC, AngII caused a decrease in AT1- and AT2-binding sites and their corresponding messenger RNAs (mRNAs), but with different kinetics [12].

Anatomical context of AGTR1

• In COS-7 cells transfected with the rat AT1 receptor, AII caused 2-3-fold enhancement of the ACTH-induced cAMP response, an effect that was partially reproduced by PMA [13].
• The present study examined the effect of endogenous and exogenous AngII on bovine aortic endothelial cells possessing both AT-1 and AT-2 receptors [14].
• The actions of circulating angiotensin II (Ang II) are mediated by the activation of the Ang II type 1 (AT1) receptor on the adrenal cortex [15].
• The nonpalmitoylated analogue retained one-third of Ang's affinity toward the AT1 receptor on bovine adrenal cortex membranes, and the palmitoylated analogue was essentially inactive [16].
• In the maternal part of the placentome, mainly AT1 receptors but also low densities of AT2 receptors and non-AT1/non-AT2 Ang II binding sites were found close to the stalk and at the main branches of the maternal crypts [17].

Associations of AGTR1 with chemical compounds

• Inhibition of IAC in AZF cells appears to occur through a novel signaling pathway, which may include a losartan-sensitive AT1 receptor coupled through a pertussis-insensitive G protein to a staurosporine-sensitive protein kinase [6].
• Although mediated through an AT1 receptor, several lines of evidence indicated that AII inhibition of IAC occurred through an unusual phospholipase C (PLC)-independent pathway [6].
• Apparently, the mechanism linking AT1 receptors to IAC inhibition and Ca2+ influx in adrenocortical cells is separate from that involving inositol trisphosphate-stimulated Ca2+ release from intracellular stores [6].
• This effect of AII was dose-dependent and was blocked by [Sar1,IIe8] AII and the nonpeptide antagonist DuP 753, indicating that it is mediated by the AT1 subtype of the AII receptor [9].
• Another and more potent AT1 receptor antagonist, L158,809, showed significant inhibition at 100 nmol/L, and at 10 mumol/L it inhibited basal aldosterone secretion (from 144.7 +/- 18.2 to 83.4 +/- 17.1 pg/10(6) cells per hour; 42% inhibition) [15].

Analytical, diagnostic and therapeutic context of AGTR1

• Our results demonstrate that AII stimulates adrenal cortical arterial dilation through endothelial cell AT2 receptor activation and NO release and AT1 receptor-dependent constriction [18].
• Western immunoblot of arterial homogenates and endothelial and zona glomerulosa cell lysates revealed 48-kD and 50-kD bands corresponding to AT1 and AT2 receptors, respectively, in all three and a 140-kD band corresponding to endothelial NO synthase in endothelial cells and arteries [18].
• Molecular cloning and characterization of the promoter for human type-1 angiotensin II receptor gene [19].
• We have applied photoaffinity labelling methods combined with site-directed mutagenesis towards the two principal angiotensin II (AnglI) receptors AT1 and AT2 in order to determine contact points between AngII and the two receptors [20].
• This has been used as a probe on Northern blots to detect changes in the levels of AT1 receptor mRNA in primary cultures of bovine zona fasciculata cells in response to activation of several different signal transduction mechanisms in addition to two major adrenal steroid products, cortisol and aldosterone [21].

References