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Chemical Compound Review

AC1NSKGQ     (3S)-9-[(4-dimethylamino-3- methyl...

Synonyms: CHEMBL321820, SureCN668525, CHEBI:61014, QC-5343, PD-123319, ...
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Disease relevance of PD123319

  • Treatment with an AT1-R antagonist, TCV116, for 20 weeks inhibited progression of interstitial fibrosis by 28%, whereas with 44-week PD123319 treatment but not 20-week treatment, the extent of the fibrous region was increased significantly, by 29% [1].
  • Conversely, the AT2 receptor antagonist PD123319 had no effect on Ang II-induced hypertrophy [2].
  • VEGF and VEGF-R2 mRNA were increased in ROP and localized to blood vessels, ganglion cells, and the inner nuclear layer, and were decreased by PD123319 [3].
  • Stimulation of the AT2 receptor in these VSMC-AT2 cells resulted in a significant (1.3-fold) increase in proteoglycan synthesis, which was abolished by the AT2 receptor antagonist, PD123319, and attenuated by pretreatment with pertussis toxin [4].
  • Increased proteinuria in STNx rats was reduced by PD123319 but to a lesser degree when compared with valsartan [5].

Psychiatry related information on PD123319


High impact information on PD123319

  • This dilation was completely abolished by pretreatment with an AT2 receptor antagonist PD123319 (10(-7) M, n = 6), suggesting that activation of AT2 receptor causes vasodilation in Af-Arts [8].
  • Angiotensin II caused concentration-dependent contractions in vitro, which were inhibited by the AT(1) receptor antagonist losartan but not by the Angiotensin II type 2 receptor antagonist PD123319 [9].
  • In the knockout mice ARBs led to significantly less cortical COX-2 elevation, which was not attenuated by PD123319 [10].
  • Ang II did not affect DNA synthesis but stimulated [3H]proline incorporation in cardiac fibroblasts (20.0+/-4.0% increase above control by 10 micromol/L; P<0.05, n=7), which was abolished by losartan 10 micromol/L but not PD123319 1 micromol/L [11].
  • Using the cardiac fibroblasts expressing AT2-R, we found that Ang II stimulated net collagenous protein production by 48% and pretreatment with an AT2-R antagonist, PD123319, evoked a further elevation (83%) [1].

Chemical compound and disease context of PD123319


Biological context of PD123319


Anatomical context of PD123319


Associations of PD123319 with other chemical compounds

  • One to two days after surgery to implant catheters and nerve electrodes, baroreflex curves were produced before and 40 minutes after intravenous administration of the AT1 antagonist losartan (10 mg/kg) or the AT2 antagonist PD123319 (500 micrograms/kg + 50 [26].
  • We found that ramipril and the AT(1) receptor blocker losartan increased COX-2 mRNA and COX-2 immunoreactivity in the macula densa approximately 4-fold, whereas the AT(2) blocker PD123319 showed no effect [27].
  • Animals were treated with AT(1) (candesartan) and/or AT(2) (PD123319) receptor antagonists, a calcium channel blocker, or vehicle (treatment periods: day -7 before to week 24 after transplantation (long term), week 12 to week 24 (late), day -7 to day +5 (early)) and observed the animals for 24 weeks [28].
  • Affinity purification in the presence of the peptide and nonpeptide AT2-receptor antagonists CGP42112A and PD123319 also resulted in elution of the same 66-kDa protein, but unlike that in the presence of Sar1,Ile8-AngII, some of the high molecular weight site was observed as well [29].
  • Vasodilatory responses to Ang II (10-10 mol/l) were performed in norepinephrine pre-contracted vessels +/- valsartan(10 mol/l), PD123319 (10 mol/l, an AT2R antagonist) or fasudil (10 mol/l) [30].

Gene context of PD123319


Analytical, diagnostic and therapeutic context of PD123319


  1. Angiotensin type 2 receptors are reexpressed by cardiac fibroblasts from failing myopathic hamster hearts and inhibit cell growth and fibrillar collagen metabolism. Ohkubo, N., Matsubara, H., Nozawa, Y., Mori, Y., Murasawa, S., Kijima, K., Maruyama, K., Masaki, H., Tsutumi, Y., Shibazaki, Y., Iwasaka, T., Inada, M. Circulation (1997) [Pubmed]
  2. Angiotensin II stimulation in vitro induces hypertrophy of normal and postinfarcted ventricular myocytes. Liu, Y., Leri, A., Li, B., Wang, X., Cheng, W., Kajstura, J., Anversa, P. Circ. Res. (1998) [Pubmed]
  3. Retinal angiogenesis is mediated by an interaction between the angiotensin type 2 receptor, VEGF, and angiopoietin. Sarlos, S., Rizkalla, B., Moravski, C.J., Cao, Z., Cooper, M.E., Wilkinson-Berka, J.L. Am. J. Pathol. (2003) [Pubmed]
  4. Regulation of vascular proteoglycan synthesis by angiotensin II type 1 and type 2 receptors. Shimizu-Hirota, R., Sasamura, H., Mifune, M., Nakaya, H., Kuroda, M., Hayashi, M., Saruta, T. J. Am. Soc. Nephrol. (2001) [Pubmed]
  5. Angiotensin type 2 receptor antagonism confers renal protection in a rat model of progressive renal injury. Cao, Z., Bonnet, F., Candido, R., Nesteroff, S.P., Burns, W.C., Kawachi, H., Shimizu, F., Carey, R.M., De Gasparo, M., Cooper, M.E. J. Am. Soc. Nephrol. (2002) [Pubmed]
  6. Role of brain angiotensin in thirst and sodium appetite of rats. Weisinger, R.S., Blair-West, J.R., Burns, P., Denton, D.A., Tarjan, E. Peptides (1997) [Pubmed]
  7. Angiotensin AT1 and AT2 receptors contribute to drinking elicited by eating in rats. Kraly, F.S., Tribuzio, R.A., Kim, Y.M., Keefe, M.E., Braun, C.J., Newman, B.H. Physiol. Behav. (1995) [Pubmed]
  8. Possible role of P-450 metabolite of arachidonic acid in vasodilator mechanism of angiotensin II type 2 receptor in the isolated microperfused rabbit afferent arteriole. Arima, S., Endo, Y., Yaoita, H., Omata, K., Ogawa, S., Tsunoda, K., Abe, M., Takeuchi, K., Abe, K., Ito, S. J. Clin. Invest. (1997) [Pubmed]
  9. Actions by angiotensin II on esophageal contractility in humans. Casselbrant, A., Edebo, A., Wennerblom, J., Lönroth, H., Helander, H.F., Vieth, M., Lundell, L., Fändriks, L. Gastroenterology (2007) [Pubmed]
  10. Renal cortical cyclooxygenase 2 expression is differentially regulated by angiotensin II AT1 and AT2 receptors. Zhang, M.Z., Yao, B., Cheng, H.F., Wang, S.W., Inagami, T., Harris, R.C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. Expression of functional angiotensin-converting enzyme and AT1 receptors in cultured human cardiac fibroblasts. Hafizi, S., Wharton, J., Morgan, K., Allen, S.P., Chester, A.H., Catravas, J.D., Polak, J.M., Yacoub, M.H. Circulation (1998) [Pubmed]
  12. Developmental regulation of angiotensin type 1 and 2 receptor gene expression and heart growth. Everett, A.D., Fisher, A., Tufro-McReddie, A., Harris, M. J. Mol. Cell. Cardiol. (1997) [Pubmed]
  13. Regulation of angiogenic factors in angiotensin II infusion model in association with tubulointerstitial injuries. Kitayama, H., Maeshima, Y., Takazawa, Y., Yamamoto, Y., Wu, Y., Ichinose, K., Hirokoshi, K., Sugiyama, H., Yamasaki, Y., Makino, H. Am. J. Hypertens. (2006) [Pubmed]
  14. Effect of intranasal administration of CV-11974, a type 1 angiotensin II receptor antagonist, on airway hyperresponsiveness and airway inflammation induced by antigen inhalation in guinea pigs. Myou, S., Fujimura, M., Kita, T., Watanabe, K., Hirose, T., Tachibana, H., Ishiura, Y., Nakao, S. Int. Arch. Allergy Immunol. (2002) [Pubmed]
  15. Growth response of human coronary smooth muscle cells to angiotensin II and influence of angiotensin AT1 receptor blockade. Hafizi, S., Chester, A.H., Allen, S.P., Morgan, K., Yacoub, M.H. Coron. Artery Dis. (1998) [Pubmed]
  16. Molecular mechanism of fibronectin gene activation by cyclic stretch in vascular smooth muscle cells. Tamura, K., Chen, Y.E., Lopez-Ilasaca, M., Daviet, L., Tamura, N., Ishigami, T., Akishita, M., Takasaki, I., Tokita, Y., Pratt, R.E., Horiuchi, M., Dzau, V.J., Umemura, S. J. Biol. Chem. (2000) [Pubmed]
  17. Increased renal vascular endothelial growth factor and angiopoietins by angiotensin II infusion is mediated by both AT1 and AT2 receptors. Rizkalla, B., Forbes, J.M., Cooper, M.E., Cao, Z. J. Am. Soc. Nephrol. (2003) [Pubmed]
  18. Attenuation of angiotensin II-mediated coronary vasoconstriction and vasodilatory action of angiotensin-converting enzyme inhibitor in pacing-induced heart failure in dogs. Oikawa, Y., Maehara, K., Saito, T., Tamagawa, K., Maruyama, Y. J. Am. Coll. Cardiol. (2001) [Pubmed]
  19. Angiotensin II activates programmed myocyte cell death in vitro. Cigola, E., Kajstura, J., Li, B., Meggs, L.G., Anversa, P. Exp. Cell Res. (1997) [Pubmed]
  20. Angiotensin in the nucleus tractus solitarii contributes to neurogenic hypertension caused by chronic nitric oxide synthase inhibition. Eshima, K., Hirooka, Y., Shigematsu, H., Matsuo, I., Koike, G., Sakai, K., Takeshita, A. Hypertension (2000) [Pubmed]
  21. Type 1 angiotensin II receptor antagonism reduces antigen-induced airway reactions. Myou, S., Fujimura, M., Kurashima, K., Tachibana, H., Watanabe, K., Hirose, T. Am. J. Respir. Crit. Care Med. (2000) [Pubmed]
  22. Angiotensin II type 1 receptor-mediated peroxide production in human macrophages. Yanagitani, Y., Rakugi, H., Okamura, A., Moriguchi, K., Takiuchi, S., Ohishi, M., Suzuki, K., Higaki, J., Ogihara, T. Hypertension (1999) [Pubmed]
  23. Cysteinyl leukotrienes are involved in angiotensin II-induced contraction of aorta from spontaneously hypertensive rats. Stanke-Labesque, F., Devillier, P., Veitl, S., Caron, F., Cracowski, J.L., Bessard, G. Cardiovasc. Res. (2001) [Pubmed]
  24. Angiotensin II dilates bovine adrenal cortical arterioles: role of endothelial nitric oxide. Gauthier, K.M., Zhang, D.X., Edwards, E.M., Holmes, B., Campbell, W.B. Endocrinology (2005) [Pubmed]
  25. Minocycline treatment attenuates microglia activation and non-angiotensin II [125I] CGP42112 binding in brainstem following nodose ganglionectomy. Roulston, C.L., Lawrence, A.J., Widdop, R.E., Jarrott, B. Neuroscience (2005) [Pubmed]
  26. Sodium intake, angiotensin II receptor blockade, and baroreflex function in conscious rats. Xu, L., Brooks, V.L. Hypertension (1997) [Pubmed]
  27. Inhibition of the renin-angiotensin system upregulates cyclooxygenase-2 expression in the macula densa. Wolf, K., Castrop, H., Hartner, A., Goppelt-Strübe, M., Hilgers, K.F., Kurtz, A. Hypertension (1999) [Pubmed]
  28. Angiotensin type 1 and type 2 receptor blockade in chronic allograft nephropathy. Lutz, J., Risch, K., Liu, S., Antus, B., Schmaderer, C., Roos, M., Ouyang, N., Lehmann, M., Heemann, U. Kidney Int. (2006) [Pubmed]
  29. Affinity purification of angiotensin type 2 receptors from N1E-115 cells: evidence for agonist-induced formation of multimeric complexes. Siemens, I.R., Yee, D.K., Reagan, L.P., Fluharty, S.J. J. Neurochem. (1994) [Pubmed]
  30. Negative regulation of RhoA/Rho kinase by angiotensin II type 2 receptor in vascular smooth muscle cells: role in angiotensin II-induced vasodilation in stroke-prone spontaneously hypertensive rats. Savoia, C., Tabet, F., Yao, G., Schiffrin, E.L., Touyz, R.M. J. Hypertens. (2005) [Pubmed]
  31. Role of AT2 receptors in angiotensin II-stimulated contraction of small mesenteric arteries in young SHR. Touyz, R.M., Endemann, D., He, G., Li, J.S., Schiffrin, E.L. Hypertension (1999) [Pubmed]
  32. Angiotensin II induces fibronectin expression in human peritoneal mesothelial cells via ERK1/2 and p38 MAPK. Kiribayashi, K., Masaki, T., Naito, T., Ogawa, T., Ito, T., Yorioka, N., Kohno, N. Kidney Int. (2005) [Pubmed]
  33. Angiotensin II stimulates DNA and protein synthesis in vascular smooth muscle cells from human arteries: role of extracellular signal-regulated kinases. Touyz, R.M., Deng, L.Y., He, G., Wu, X.H., Schiffrin, E.L. J. Hypertens. (1999) [Pubmed]
  34. STAT proteins mediate angiotensin II-induced production of TIMP-1 in human proximal tubular epithelial cells. Chen, X., Wang, J., Zhou, F., Wang, X., Feng, Z. Kidney Int. (2003) [Pubmed]
  35. Signal transduction mediated by angiotensin II receptor subtypes expressed in rat renal mesangial cells. Madhun, Z.T., Ernsberger, P., Ke, F.C., Zhou, J., Hopfer, U., Douglas, J.G. Regul. Pept. (1993) [Pubmed]
  36. Effects of intracerebroventricular injections of losartan or PD123319 on arterial pressure and heart rate of sodium replete and sodium deplete rats. De Luca, L.A., Barbosa, S.P., Sugawara, A.M., Menani, J.V. Regul. Pept. (1996) [Pubmed]
  37. Acute sodium depletion modifies septo-preoptic neuron sensitivities to neurohormones. Liénard, F., Galaverna, O., Thornton, S.N., Meile, M.J., Nicolaïdis, S. Brain Res. (1998) [Pubmed]
  38. Angiotensin II actions in paraventricular nucleus: functional evidence for neurotransmitter role in efferents originating in subfornical organ. Bains, J.S., Potyok, A., Ferguson, A.V. Brain Res. (1992) [Pubmed]
  39. Evidence that prostaglandins mediate the antihypertensive actions of angiotensin-(1-7) during chronic blockade of the renin-angiotensin system. Iyer, S.N., Yamada, K., Diz, D.I., Ferrario, C.M., Chappell, M.C. J. Cardiovasc. Pharmacol. (2000) [Pubmed]
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