Non-peptide AT2-receptor agonists

Current Opinion in Pharmacology

Volumn 11, Issue 2, 2011, Pages 187-192

  Steckelings, U Muscha ^a   Larhed, Mats ^b   Hallberg, Anders ^b   Widdop, Robert E ^c   Jones, Emma S ^c   Wallinder, Charlotta ^b   Namsolleck, Pawel ^a   Dahlöf, Björn ^d   Unger, Thomas ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b UPPSALA UNIVERSITY   (Sweden)

^c MONASH UNIVERSITY   (Australia)

^d SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; ANGIOTENSIN 1 RECEPTOR; ANGIOTENSIN 2 RECEPTOR; ANGIOTENSIN 2 RECEPTOR AGONIST; CASPASE 3; COMPOUND 21; DOPAMINE; FAS LIGAND; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 6; MONOCYTE CHEMOTACTIC PROTEIN 1; NICOTINOYLTYROSYL(N BENZYLOXYCARBONYLARGINYL)LYSYLHISTIDYLPROLYLISOLEUCINE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ARTICLE; BINDING AFFINITY; BRAIN INFARCTION; BRAIN ISCHEMIA; CYTOKINE PRODUCTION; DOPAMINE METABOLISM; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; HEART INFARCTION; HYPERTENSION; NERVE REGENERATION; NEUROPROTECTION; NONHUMAN; PLASMA RENIN ACTIVITY; PRIORITY JOURNAL; PROTEINURIA; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM;

EID: 79954416372     PISSN: 14714892     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coph.2010.11.002     Document Type: Review

References (38)

1. A.T. Chiu, W.F. Herblin, D.E. McCall, R.J. Ardecky, D.J. Carini, J.V. Duncia, L.J. Pease, P.C. Wong, R.R. Wexler, and A.L. Johnson Identification of angiotensin II receptor subtypes Biochem Biophys Res Commun 165 1989 196 203 (Pubitemid 20012475)
2. S. Whitebread, M. Mele, B. Kamber, and M. de Gasparo Preliminary biochemical characterization of two angiotensin II receptor subtypes Biochem Biophys Res Commun 163 1989 284 291 (Pubitemid 19227303)
3. P.B.M.W. Timmermans, P.C. Wong, A.T. Chiu, W.F. Herblin, P. Benfield, D.J. Carin, R.J. Lee, R.R. Wexler, J.A. Saye, and R.D. Smith Angiotensin II receptors and angiotensin II receptor antagonists Pharmacol Rev 45 1993 205 251 (Pubitemid 23191415)
4. M. de Gasparo, K.J. Catt, T. Inagami, J.W. Wright, and T. Unger International union of pharmacology. XXIII. The angiotensin II receptors Pharmacol Rev 52 2000 415 472
5. M. Nakajima, M. Mukoyama, R.E. Pratt, M. Horiuchi, and V.J. Dzau Cloning of cDNA and analysis of the gene for mouse angiotensin II type 2 receptor Biochem Biophys Res Commun 197 1993 393 399 (Pubitemid 24034583)
6. H. Matsubara, T. Sugaya, S. Murasawa, Y. Nozawa, Y. Mori, H. Masaki, K. Maruyama, Y. Tsutumi, Y. Shibasaki, and Y. Moriguchi Tissue-specific expression of human angiotensin II AT1 and AT2 receptors and cellular localization of subtype mRNAs in adult human renal cortex using in situ hybridization Nephron 80 1998 25 34 (Pubitemid 28434688)
7. T. Unger The angiotensin type 2 receptor: variations on an enigmatic theme J Hypertens 17 1999 1775 1786 (Pubitemid 30345311)
8. C.J. Wruck, H. Funke-Kaiser, T. Pufe, H. Kusserow, M. Menk, J.H. Schefe, M.L. Kruse, M. Stoll, and T. Unger Regulation of transport of the angiotensin AT2 receptor by a novel membrane-associated Golgi protein Arterioscler Thomb Vasc Biol 25 2005 57 64 (Pubitemid 40054254)
9. H. Funke-Kaiser, J. Reinemund, U.M. Steckelings, and T. Unger Adapter proteins and promoter regulation of the angiotensin AT2 receptor - implications for cardiac pathophysiology J Renin Angiotensin Aldosterone Syst 11 2010 7 17
10. M. Stoll, U.M. Steckelings, M. Paul, S.P. Bottari, R. Metzger, and T. Unger The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells J Clin Invest 95 1995 651 657
11. R. Lucius, S. Gallinat, Rosenstiel, T. Herdegen, J. Sievers, and T. Unger The angiotensin II type 2 (AT2) receptor promotes axonal regeneration in the optic nerve of adults rats J Exp Med 188 1998 661 670 (Pubitemid 28387929)
12. F. Rompe, T. Unger, and U.M. Steckelings The angiotensin AT2 receptor in inflammation Drug News Perspect 23 2010 104 111
13. 1 ligands: susceptibility to receptor mutations Mol Pharmacol 51 1997 301 311 (Pubitemid 27074152)
14. S.D. Kivlighn, W.R. Huckle, G.J. Zingaro, R.A. Rivero, V.J. Lotti, R.S.L. Chang, T.W. Schorn, N. Kevin, and R.G. Johnson Jr. Discovery of L-162,313: a nonpeptide that mimics the biological actions of angiotensin II Am J Physiol 268 1995 R820 R823
15. 1 receptor J Biol Chem 270 1995 1493 1496
16. 2 receptor agonist in vivo J Med Chem 47 2004 1536 1546 (Pubitemid 38327477)
17. Y. Wan, C. Wallinder, B. Plouffe, H. Beaudry, A.K. Mahalingam, X. Wu, B. Johansson, M. Holm, M. Botros, and A. Karlén Design, synthesis, and biological evaluation of the first selective nonpeptide AT2 receptor agonist J Med Chem 47 2004 5995 6008 This is the first description of a non-peptide AT2-receptor agonist. (Pubitemid 39507341)
18. D. Henrion, N. Kubis, and B.I. Lévy Physiological and pathophysiological functions of the AT(2) subtype receptor of angiotensin II: from large arteries to the microcirculation Hypertension 38 2001 1150 1157 (Pubitemid 34252821)
19. R.E. Widdop, K. Matrougui, B.I. Levy, and D. Henrion AT2 receptor-mediated relaxation is preserved after long-term AT1 receptor blockade Hypertension 40 2002 516 520
20. S. Bosnyak, I.K. Welungoda, A. Hallberg, M. Alterman, R.E. Widdop, and E.S. Jones Stimulation of angiotensin AT2 receptors by the non-peptide agonist, compound 21, evokes vasodepressor effects in conscious spontaneously hypertensive rats Br J Pharmacol 159 2010 709 716 This is the first study looking at the impact of direct AT2R-stimulation with C21 on vasodilation and blood-pressure regulation. The authors show that C21 evoked dose-dependent vasorelaxations in aortic and mesenteric vessels, but lowered blood pressure in SHR only under concomitant AT1R-blockade.
21. M.N. Barber, D.B. Sampey, and R.E. Widdop AT2 receptor stimulation enhances antihypertensive effect of AT1 receptor antagonist in hypertensive rats Hypertension 34 1999 1112 1116
22. X.C. Li, and R.E. Widdop AT2 receptor-mediated vasodilatation is unmasked by AT1 receptor blockade in conscious SHR Br J Pharmacol 142 2004 821 830 (Pubitemid 38998096)
23. R.M. Carey, N.L. Howell, X.H. Jin, and H.M. Siragy Angiotensin type 2 receptor-mediated hypotension in angiotensin type-1 receptor-blocked rats Hypertension 38 2001 1272 1277 (Pubitemid 34033401)
24. T. Ichiki, P.A. Labosky, C. Shiota, S. Okuyama, Y. Imagawa, A. Fogo, F. Niimura, I. Ichikawa, B.L. Hogan, and T. Inagami Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor Nature 377 1995 748 750
25. L. Hein, G.S. Barsh, R.E. Pratt, V.J. Dzau, and B.K. Kobilka Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice Nature 377 1995 744 747
26. Y. Tsutsumi, H. Matsubara, H. Masaki, H. Kurihara, S. Murasawa, S. Takai, M. Miyazaki, Y. Nozawa, R. Ozono, and K. Nakagawa Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation J Clin Invest 104 1999 925 935 (Pubitemid 29536342)
27. T. Masaki, A. Kurihara, N. Yamaki, N. Inomata, Y. Nozawa, Y. Mori, S. Murasawa, K. Kizima, K. Maruyama, and M. Horiuchi Cardiac-specific overexpression of angiotensin II AT2 receptor causes attenuated response to AT1 receptor-mediated pressor and chronotropic effects J Clin Invest 101 1998 527 535 (Pubitemid 28084234)
28. E. Kaschina, A. Grzesiak, J. Li, A. Foryst-Ludwig, M. Timm, F. Rompe, M. Sommerfeld, U.R. Kemnitz, C. Curato, and P. Namsolleck AT2-receptor stimulation: a novel option of therapeutic interference with the renin-angiotensin-system in myocardial infarction? Circulation 118 2008 2523 2532 This is the first experimental study using C21 for AT2R-stimulation in vivo. Treatment of rats with C21 after myocardial infarction reduced scar size, improved cardiac function and ameliorated the inflammatory response in the peri-infarct tissue.
29. P. Gelosa, A. Pignieri, L. Fändriks, M. de Gasparo, A. Hallberg, C. Banfi, L. Castiglioni, L. Turolo, U. Guerrini, and E. Tremoli Stimulation of AT2 receptor exerts beneficial effects in stroke-prone rats: focus on renal damage J Hypertens 27 2009 2444 2451 This study looked at the effect of AT2R-stimulation with C21 on hypertension-induced renal and cerebral damage in SHR-SP. The authors report that C21 attenuated renal structural changes and inflammation and delayed the occurrence of brain abnormalities, both in a blood-pressure independent manner.
30. U.M. Steckelings, R.E. Widdop, L. Paulis, and T. Unger The angiotensin AT2 receptor in left ventricular hypertrophy J Hypertens 28 Suppl. 1 2010 S50 55
31. M. Iwai, H.W. Liu, R. Chen, A. Ide, S. Okamoto, R. Hata, M. Sakanaka, T. Shiuchi, and M. Horiuchi Possible inhibition of focal cerebral ischemia by angiotensin II type 2 receptor stimulation Circulation 110 2004 843 848 (Pubitemid 39096013)
32. C.A. McCarthy, A. Vinh, J.K. Callaway, and R.E. Widdop Angiotensin AT2 receptor stimulation causes neuroprotection in a conscious rat model of stroke Stroke 40 2009 1482 1489 This is the first study that has shown direct AT2 receptor stimulation is neuroprotective in an experimental model of stroke, and thus provides proof of principle for the AT2 receptor as a therapeutic target in neuroprotection.
33. K. Reinecke, R. Lucius, A. Reinecke, U. Rickert, T. Herdegen, and T. Unger Angiotensin II accelerates functional recovery in the rat sciatic nerve in vivo: role of the AT2 receptor and the transcription factor NF-κB FASEB J 17 2003 2094 2096
34. B. Mertens, P. Vanderheyden, Y. Michotte, and S. Sarre Direct angiotensin II type 2 receptor stimulation decreases dopamine synthesis in the rat striatum Neuropharmacology 58 2010 1038 1044 This study reports the inhibition of dopamine synthesis in rats after local application of C21 into the striatum.
35. M. Horiuchi, W. Hayashida, M. Akishita, K. Tamura, L. Daviet, J.Y. Lehtonen, and V.J. Dzau Stimulation of different subtypes of angiotensin II receptors, AT1 and AT2 receptors, regulates STAT activation by negative crosstalk Circ Res 84 1999 876 882 (Pubitemid 29196731)
36. L. Wu, M. Iwai, Z. Li, T. Shiuchi, L.-J. Min, T.-X. Cui, J.-M. Li, M. Okumura, C. Nahmias, and M. Horiuchi Regulation of inhibitory protein-κB and monocyte chemoattractant protein-1 by angiotensin II type 2 receptor activated Src homology protein tyrosine phosphatase-1 in fetal vascular smooth muscle cells Mol Endocrinol 18 2004 666 678 (Pubitemid 38328210)
37. F. Rompe, M. Artuc, A. Hallberg, M. Alterman, K. Ströder, C. Thöne-Reineke, A. Reichenbach, J. Schacherl, B. Dahlöf, and M. Bader Direct angiotensin II type 2 receptor stimulation acts anti-inflammatory through epoxyeicosatrienoic acid and inhibition of nuclear factor kappaB Hypertension 55 2009 924 931 This study confirms the specific, AT2R-agonistic property of C21 for example by showing the absence of effects in AT2R-deficient cells. It furthermore provides evidence for the anti-inflammatory effect of C21 in vitro and in vivo and describes phosphatase and CYP2C/2J activation as well as NF-κB inhibition as underlying mechanisms.
38. K. Node, Y. Huo, X. Ruan, B. Yang, M. Spiecker, K. Ley, D.C. Zeldin, and J.M. Liao Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids Science 285 1999 1276 1279 (Pubitemid 29398616)