The Angiotensin Type 1 and Type 2 Receptor Families

Siblings or Cousins?
  • Steven J. Fluharty
  • Lawrence P. Reagan
  • Daniel K. Yee
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 377)


Angiotensin II (AngII) is one of the key hormones involved in the regulation of cardiovascular and body fluid homeostasis. Several naturally occurring stimuli such as hypovolemia, hyponatremia and hypotension are well known to activate the renin-angiotensin system (RAS) (cf. (1)). The rate-limiting step in the synthesis of AngII is the release of renin from the juxtaglomerular cells of the kidney. Renin converts the plasma α-globulin protein angiotensinogen to AngI, which subsequently is converted to AngII by a carboxyl dipeptidase known as angiotensin converting enzyme. AngII has numerous peripheral target organs and actions including vasoconstriction, aldosterone release, and augmentation of sympathetic nervous system function. Circulating AngII also has important central nervous system (CNS) effects although, like the other peptide hormones, it has restricted access to most cerebral structures because of the blood-brain barrier. However, by acting on the circumventricular organs (CVOs) that possess fenestrated capillaries, blood-borne AngII can act centrally to regulate pituitary function, elicit a central pressor response that likely involves descending activation of the sympathetic nervous system, and stimulate thirst and salt appetite (cf. (2)). In addition to the well-established peripheral RAS, AngII and related smaller peptides also can be directly generated in the CNS where the peptide appears to participate in the regulation of cerebral blood flow, neurohypophysial hormone release, and in the pathophysiology of some forms of hypertension (2–4).


Receptor Subtype Inferior Olive Quantitative Autoradiography Medial Geniculate Nucleus Adult Human Kidney 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Peach MJ, Renin-angiotensin system: Biochemistry and mechanism of action. Physiol Rev 1977; 57: 313–370.PubMedGoogle Scholar
  2. 2.
    Phillips MI, Angiotensin in the brain. Neuroendocrinology 1978; 25: 354–377.PubMedCrossRefGoogle Scholar
  3. 3.
    Ganten D, Fuxe MI, Phillips MI, Mann JFE, Ganten U. The brain isorenin-angiotensin system: biochemistry, localization, and possible role in drinking and blood pressure regulation. Frontiers in Neuroendocrinology Raven Press N Y 1978;Vol 5:61–99.Google Scholar
  4. 4.
    Naveri L, Stromberg C, Saavedra JM, Angiotensin II AT2 receptor stimulation extends the upper limit of cerebral blood flow autoregulation: agonist effects of CGP 42112 and PD 123319. J Cereb Blood Flow & Metab 1994; 14: 38–44.CrossRefGoogle Scholar
  5. 5.
    Bottari SP, Taylor V, King IN, Bogdal Y, Whitebread S, DeGasparo M, Angitoensin II AT2 receptors do not interact with guanine nucleotide binding proteins. Eur J Pharmacol 1991; 207: 157–163.PubMedCrossRefGoogle Scholar
  6. 6.
    Bumpus FM, Catt KJ, Chiu AT, DeGasparo M, Goodfriend T, Husain A, Peach MJ, Taylor DG Jr, Timmermans PB. Nomenclature for angiotensin receptors. A report of the Nomenclature Committee of the Council for High Blood Pressure Research. Hypertension 1991; 17: 720–721.Google Scholar
  7. 7.
    Chiu AT, McCall DE, Nguyen TT, Carini DJ, Duncia JV, Herblin WF, Uyeda RT, Wong PC, Wexler RR, Johnson AL, Timmermans PBMWM. Discrimination of angiotensin II receptor subtypes by dithiothreitol. Eur J Pharmacol 1989; 170: 117–118.PubMedCrossRefGoogle Scholar
  8. 8.
    Dudley DT, Panek RL, Major TC, Lu GH, Bruns RF, Klinkefus BA, Hodges JC, Weishaar RE, Subclasses of angiotensin II binding sites and their functional significance. Mol Pharmacol 1990; 38: 370–377.PubMedGoogle Scholar
  9. 9.
    Widdowson PS, Renouard A, Vilaine J-P. Binding of [3H]angiotensin II and [3H]DuP 753 (Losartan) to rat liver homogenates reveals multiple sites. Relationship to ATla-and AT1b-type angiotensin receptors and novel nonangiotensin binding sites. Peptides 1993; 14: 829–837.Google Scholar
  10. 10.
    Sechi LA, Grady EF, Griffin CA, Kalinyak JE, Schambelan M, Distribution of angiotensin II receptor subtypes in rat and human kidney. Am J Physiol Renal, Fluid Electrolyte Physiol 1992; 262: F236–F240.Google Scholar
  11. 11.
    Gröne H-J, Simon M, Fuchs E, Autoradiographic characterization of angiotensin receptor subtypes in fetal and adult human kidney. Am J Physiol Renal, Fluid Electrolyte Physiol 1992; 262: F326–F331.Google Scholar
  12. 12.
    Herblin WF, Diamond SM, Timmermans PBMWM. Localization of angiotensin II receptor subtypes in the rabbit adrenal and kidney. Peptides 1991; 12: 581–584.PubMedCrossRefGoogle Scholar
  13. 13.
    Chang RSL, Lotti VJ, Two distinct angiotensin II receptor binding sites in rat adrenal revealed by new selective nonpeptide ligands. Mol Pharmacol 1990; 29: 347–351.Google Scholar
  14. 14.
    Chiu AT, Herblin WF, McCall DE, Ardecky RJ, Carini DJ, Duncia JV, Pease LJ, Wong PC, Wexler RR, Johnson AL, Timmermans PBMWM, Identification of angiotensin II receptor subtypes. Biochem Biophys Res Commun 1989; 165: 196–203.PubMedCrossRefGoogle Scholar
  15. 15.
    Feolde E, Vigne P, Frelin C, Angiotensin AT1 receptors mediate a positive inotropic effect of angiotensin II in guinea pig atria. Eur J Pharmacol Mol Pharmacol 1993; 245: 63–66.CrossRefGoogle Scholar
  16. 16.
    Saavedra JM, Viswanathan M, Shigematsu K, Localization of angiotensin AT1 receptors in the rat heart conduction system. Eur J Pharmacol 1993; 235: 301–303.PubMedCrossRefGoogle Scholar
  17. 17.
    Sechi LA, Griffin CA, Grady EF, Kalinyak JE, Schambelan M, Characterization of angiotensin II receptor subtypes in rat heart. Circ Res 1992; 71: 1482–1489.PubMedCrossRefGoogle Scholar
  18. 18.
    Pucell AG, Hodges JC, Sen I, Bumpus FM, Husain A. Biochemical properties of the ovarian granulosa cell type 2-angiotensin II receptor. Endocrinology 1991; 128: 1947–1959.PubMedCrossRefGoogle Scholar
  19. 19.
    Viswanathan M, Tsutsumi K, Correa FMA, Saavedra JM. Changes in expression of angiotensin receptor subtypes in the rat aorta during development. Biochem Biophys Res Commun 1991; 179: 1361–1367.PubMedCrossRefGoogle Scholar
  20. 20.
    Grady EF, Sechi LA, Griffin CA, Schambelan M, Kalinyak JE, Expression of AT2 receptors in the developing rat fetus. J Clin Invest 1991; 88: 921–933.PubMedCrossRefGoogle Scholar
  21. 21.
    Grady EF, Kalinyak JE, Expression of AT2 receptors in rat fetal subdermal cells. Regul Pept 1993; 44: 171–180.PubMedCrossRefGoogle Scholar
  22. 22.
    Tsutsumi K, Stromberg C, Viswanathan M, Saavedra JM. Angiotensin-II receptor subtypes in fetal tissue of the rat: autoradiography, guanine nucleotide sensitivity, and association with phosphoinositide hydrolysis. Endocrinology 1991; 129: 1075–1082.PubMedCrossRefGoogle Scholar
  23. 23.
    Aldred GP, Chai SY, Song K, Zhuo J, MacGregor DP, Mendelsohn FAO, Distribution of angiotensin II receptor subtypes in the rabbit brain. Regul Pept 1993; 44: 119–130.PubMedCrossRefGoogle Scholar
  24. 24.
    Rowe BP, Grove KL, Saylor DL, Speth RC. Discrimination of angiotensin II receptor subtype distribution in the rat brain using non-peptidic receptor antagonists. Regul Pept 1991; 33: 45–53.PubMedCrossRefGoogle Scholar
  25. 25.
    Song K, Allen AM, Paxinos G, Mendelsohn FAO, Mapping of angiotensin II receptor subtype heterogeneity in rat brain. J Comp Neurol 1992; 316: 467–484.PubMedCrossRefGoogle Scholar
  26. 26.
    Tsutsumi K, Saavedra JM, Quantitative autoradiography reveals different angiotensin II receptor subtypes in selected rat brain nuclei. J Neurochem 1991; 56: 348–351.PubMedCrossRefGoogle Scholar
  27. 27.
    Tsutsumi K, Saavedra JM, Characterization and development of angiotensin II receptor subtypes (AT1 and AT2) in rat brain. Am J Physiol 1991; 261: R209–R216.PubMedGoogle Scholar
  28. 28.
    Gehlert DR, Gackenheimer SL, Schober DA, Autoradiographic localization of subtypes of angiotensin II antagonist binding in the rat brain. Neuroscience 1991; 44: 501–514.PubMedCrossRefGoogle Scholar
  29. 29.
    Steckelings UM, Bottari SP, Unger T, Angiotensin receptor subtypes in the brain. Trends Pharmacol Sci 1992; 13: 365–368.PubMedCrossRefGoogle Scholar
  30. 30.
    Obermuller N, Unger T, Gohlke P, de Gasparo M, Bottari SP. Distribution of angiotensin II receptor subtypes in rat brain nuclei. Neurosci Lett 1991; 132: 11–15.PubMedCrossRefGoogle Scholar
  31. 31.
    Allen AM, Paxinos G, McKinley MJ, Chai SY, Mendelsohn FAO, Localization and characterization of angiotensin II receptor binding sites in the human basal ganglia, thalamus, midbrain pons, and cerebellum. J Comp Neurol 1991; 312: 291–298.PubMedCrossRefGoogle Scholar
  32. 32.
    Paxton WG, Runge M, Horaist C, Cohen C, Alexander RW, Berstein KE, Immunohistochemical localization of rat angiotensin II AT1 receptor. Am J Physiol 1993; 264: F989–F995.PubMedGoogle Scholar
  33. 33.
    Edwards RM, Stack EJ, Weidley EF, Aiyar N, Keenan RM, Hill DT, Weinstock J, Characterization of renal angiotensin II receptors using subtype selective antagonists. J Pharmacol Exp Ther 1992; 260: 933–938.PubMedGoogle Scholar
  34. 34.
    Barker S, Marchant W, Ho MM, Puddefoot JR, Hinson JP, Clark AJL, Vinson GP, A monoclonal antibody to a conserved sequence in the extracellular domain recognizes the angiotensin AT1 receptor in mammalian target tissues. J Mol Endocrinol 1993; 11: 241–245.PubMedCrossRefGoogle Scholar
  35. 35.
    Phillips MI, Shen L, Richards EM, Raizada MK, Immunohistochemical mapping of angiotensin AT1 receptors in the brain. Regul Pept 1993; 44: 95–107.PubMedCrossRefGoogle Scholar
  36. 36.
    Reagan LP, Flanagan-Cato LM, Yee DK, Ma L-Y, Sakai RR, Fluharty SJ, Immunohistochemical mapping of angiotensin type 2 (AT2) receptors in rat brain. Brain Res 1994; 662: 45–59.PubMedCrossRefGoogle Scholar
  37. 37.
    Kambayashi Y, Bardhan S, Takahashi K, Tsuzuki S, Inui H, Hamakubo T, Inagami T, Molecular cloning of a novel angiotensin II receptor isoform involved in phosphotyrosine phosphatase inhibition. J Biol Chem 1993; 268: 24543–24546.PubMedGoogle Scholar
  38. 38.
    Mukoyama M, Nakajima M, Horiuchi M, Sasamura H, Pratt RE, Dzau VJ, Expression cloning of type 2 angiotensin II receptor reveals a unique class of seven-transmembrane receptors. J Biol Chem 1993; 268: 24539–24542.PubMedGoogle Scholar
  39. 39.
    Tsutsumi K, Saavedra JM, Heterogeneity of angiotensin II AT2 receptors in the rat brain. Mol Pharmacol 1992; 41: 290–297.PubMedGoogle Scholar
  40. 40.
    Iwai N, Inagami T, Identification of two subtypes in the rat type I angiotensin II receptor. FEBS Lett 1992; 298: 257–260.PubMedCrossRefGoogle Scholar
  41. 41.
    Sasamura H, Hein L, Krieger JE, Pratt RE, Kobilka BK, Dzau VJ, Cloning, characterization, and expression of two angiotensin receptor (AT1) isoforms from the mouse genome. Biochem Biophys Res Commun 1992; 185: 253–259.PubMedCrossRefGoogle Scholar
  42. 42.
    Fluharty SJ, Reagan LP, Characterization of binding sites for the angiotensin II antagonist 1251-[Sarc1, Ile8]-angiotensin II on murine neuroblastoma N1E-115 cells. J Neurochem 1989; 52: 1393–1400.PubMedCrossRefGoogle Scholar
  43. 43.
    Mann JFE, Schiller PW, Schiffrin EL, Boucher R, Geneset J, Brain receptor binding and central actions of angiotensin analogs in rat brain. Am J Physiol 1981; 241: R124–R129.PubMedGoogle Scholar
  44. 44.
    Reagan LP, Ye XH, Mir R, DePalo LR, Fluharty SJ, Up-regulation of angiotensin II receptors by in vitro differentiation of murine N1E-115 neuroblastoma cells. Mol Pharmacol 1990; 38: 878–886.PubMedGoogle Scholar
  45. 45.
    Siemens IR, Reagan LP, Yee DK, Fluharty SJ. Isolation and Biochemical Characterization of Two Distinct Angiotensin AT2 Receptor Populations in Murine Neuroblastoma N1E-115 Cells. J Neurochem 1994;(In Press).Google Scholar
  46. 46.
    Murphy TJ, Alexander RW, Griendling KK, Runge MS, Bernstein KE, Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor. Nature 1991; 351: 233–236.PubMedCrossRefGoogle Scholar
  47. 47.
    Sasaki K, Yamano Y, Bardhan S, Iwai N, Murray JJ, Hasegawa M, Matsuda Y, Inagami T, Cloning and expression of a complementary DNA encoding a bovine adrenal angiotensin II type-1 receptor. Nature 1991; 351: 230–233.PubMedCrossRefGoogle Scholar
  48. 48.
    Kakar SS, Riel KK, Neill JD, Differential expression of angiotensin II receptor subtype mRNAs (AT-1A and AT-1B) in the brain. Biochem Biophys Res Commun 1992; 185: 688–692.PubMedCrossRefGoogle Scholar
  49. 49.
    Mauzy CA, Hwang O, Egloff AM, Wu L-H, Chung F-Z. Cloning, expression, and characterization of a gene encoding the human angiotensin II type 1a receptor. Biochem Biophys Res Commun 1992; 186: 277–284.PubMedCrossRefGoogle Scholar
  50. 50.
    Sandberg K, Ji H, Clark AJL, Shapira H, Catt KJ, Cloning and expression of a novel angiotensin II receptor subtype. J Biol Chem 1992; 267: 9455–9458.PubMedGoogle Scholar
  51. 51.
    Siemens IR, Adler HJ, Addya K, Mah SJ, Fluharty SJ, Biochemical analysis of solubilized angiotensin II receptors from murine neuroblastoma N1E-115 cells by covalent cross-linking and affinity purification. Mol Pharmacol 1991; 40: 717–726.PubMedGoogle Scholar
  52. 52.
    Siemens IR, Swanson GN, Fluharty SJ, Harding JW. Solubilization and partial characterization of angiotensin II receptors from rat brain. J Neurochem 1991; 57: 690–700.PubMedCrossRefGoogle Scholar
  53. 53.
    Siemens IR, Yee DK, Reagan LP, Fluharty SJ. Affinity Purification of Angiotensin Type 2 Receptors from N1E-115 Cells: Evidence for Agonist-Induced Formation of Multimeric Complexes. J Neurochem 1994; (In Press).Google Scholar
  54. 54.
    Yee DK, Reagan LP, Moga CN, Siemens IR, Fluharty SJ. Angiotensin II stabilizes a multimeric Type 2 (AT2) receptor complex in murine neuroblastoma N1E-115 cells. Regul Pept 1994; 54: 355–366.PubMedCrossRefGoogle Scholar
  55. 55.
    Reagan LP, Theveniau M, Yang X-D, Siemens IR, Yee DK, Reisine T, Fluharty SJ, Development of polyclonal antibodies against Angiotensin Type 2 (AT2) receptors. Proc Natl Acad Sci U S A 1993; 90: 7956–7960.PubMedCrossRefGoogle Scholar
  56. 56.
    Kambayashi Y, Bardhan S, Inagami T. Peptide growth factors markedly decrease the ligand binding of angiotensin II type 2 receptor in rat cultured vascular smooth muscle cells. Biochem Biophys Res Commun 1993; 194: 478–482.PubMedCrossRefGoogle Scholar
  57. 57.
    Bergsma DJ, Ellis C, Kumar C, Nuthulaganti P, Kersten H, Elshourbagy N, Griffin E, Stadel JM, Alyar N, Cloning and characterization of a human angiotensin II type 1 receptor. Biochem Biophys Res Commun 1992; 183: 989–995.PubMedCrossRefGoogle Scholar
  58. 58.
    Konishi H, Kuroda S, Inada Y, Fujisawa Y. Novel subtype of human angiotensin II type 1 receptor: cDNA cloning and expression. Biochem Biophys Res Commun 1994; 199: 467–474.PubMedCrossRefGoogle Scholar
  59. 59.
    Kuroda S, Konishi H, Okishio M, Fujisawa Y. Novel subtype of human angiotensin II type 1 receptor: Analysis of signal transduction mechanism in transfected Chinese hamster ovary cells. Biochem Biophys Res Commun 1994; 199: 475–487.PubMedCrossRefGoogle Scholar
  60. 60.
    Burns KD, Inagami T, Harris RC, Cloning of a rabbit kidney cortex AT1 angiotensin II receptor that is present in proximal tubule epithelium. Am J Physiol Renal, Fluid Electrolyte Physiol 1993; 264: F645–F654.Google Scholar
  61. 61.
    Itazaki K, Shigeri Y, Fujimoto M, Molecular cloning and characterization of the angiotensin receptor subtype in porcine aortic smooth muscle. Eur J Pharmacol Mol Pharmacol 1993; 245: 147–156.CrossRefGoogle Scholar
  62. 62.
    Burns L, Clark KL, Bradley J, Robertson MJ, Clark AJL, Molecular cloning of the canine angiotensin II receptor: An AT1-like receptor with reduced affinity for DuP753. FEBS Lett 1994; 343: 146–150.PubMedCrossRefGoogle Scholar
  63. 63.
    Kakar SS, Sellers JC, Devor DC, Musgrove LC, Neill JD. Angiotensin II type-1 receptor subtype cDNAs: Differential tissue expression and hormonal regulation. Biochem Biophys Res Commun 1992; 183: 1090–1096.PubMedCrossRefGoogle Scholar
  64. 64.
    Ji H, Sandberg K, Zhang Y, Catt KJ. Molecular cloning, sequencing and functional expression of an amphibian angiotensin II receptor. Biochem Biophys Res Commun 1993; 194: 756–762.PubMedCrossRefGoogle Scholar
  65. 65.
    Bergsma DJ, Ellis C, Nuthulaganti PR, Nambi P, Scaife K, Kumar C, Aiyar N, Isolation and expression of a novel angiotensin II receptor from Xenopus laevis heart. Mol Pharmacol 1993; 44: 277–284.PubMedGoogle Scholar
  66. 66.
    Murphy TJ, Nakamura Y, Takeuchi K, Alexander RW. A cloned angiotensin receptor isoform from the turkey adrenal gland is pharmacologically distinct from mammalian angiotensin receptors. Mol Pharmacol 1993;44:l–7.Google Scholar
  67. 67.
    Yamano Y, Ohyama K, Chaki S, Guo D-F, Inagami T, Identification of amino acid residues of rat angiotensin II receptor for ligand binding by site directed mutagenesis. Biochem Biophys Res Commun 1992; 187: 1426–1431.PubMedCrossRefGoogle Scholar
  68. 68.
    Khosla MC, Leese RA, Maloy WL, Ferreira AT, Smeby RR, Bumpus FM. Synthesis of some analogs of angiotensin II as specific antagonists of the parent hormone. J Med Chem 1972; 15: 792–795.PubMedCrossRefGoogle Scholar
  69. 69.
    Ji H, Leung M, Zhang Y, Catt KJ, Sandberg K, Differential structural requirements for specific binding of nonpeptide and peptide antagonists to the AT1 angiotensin receptor — Identification of amino acid residues that determine binding of the antihypertensive drug Losartan. J Biol Chem 1994; 269: 16533–16536.PubMedGoogle Scholar
  70. 70.
    Schambye HT, Hjorth SA, Bergsma DJ, Sathe G, Schwartz TW, Differentiation between binding sites for angiotensin II and nonpeptide antagonists on the angiotensin II type 1 receptors. Proc Natl Acad Sci U S A 1994; 91: 7046–7050.PubMedCrossRefGoogle Scholar
  71. 71.
    Schambye HT, Wijk BV, Hjorth SA, Wienen W, Entzeroth M, Bergsma DJ, Schwartz TW. Mutations in transmembrane segment VII of the AT1 receptor differentiate between closely related insurmountable and competitive angiotensin antagonists. Br J Pharmacol 1994; 113: 331–333.PubMedCrossRefGoogle Scholar
  72. 72.
    Kobilka BK, Kobilka TS, Daniel K, Regan JW, Caron MG, Lefkowitz RJ, Chimeric alpha-2, beta-2-adrenergic receptors: Delineation of domains involved in effector coupling and ligand binding specificity. Science 1988; 240: 1310–1316.PubMedCrossRefGoogle Scholar
  73. 73.
    Hartig P, Kao H-T, Macchi M, Adham N, Zgombic J, Weinshank R, Branchek T, The molecular biology of serotonin receptors: An overview. Neuropsychopharmacology 1990; 3: 335–347.PubMedGoogle Scholar
  74. 74.
    Strosberg AD. Structure/function relationship of proteins belonging to the family of receptors coupled to GTP-binding proteins. Eur J Biochem 1991; 196: 1–10.PubMedCrossRefGoogle Scholar
  75. 75.
    Tota MR, Candelore MR, Dixon RAF, Strader CD. Biophysical and genetic analysis of the ligand-binding site of the beta-adrenoceptor. Trends Pharmacol Sci 1991; 12: 4–6.PubMedCrossRefGoogle Scholar
  76. 76.
    Wess J, Molecular basis of muscarinic acetylcholine receptor function. Trends Pharmacol Sci 1993; 14: 308–313.PubMedCrossRefGoogle Scholar
  77. 77.
    Quehenberger O, Prossnitz ER, Cavanagh SL, Cochrane CG, Ye RD, Multiple domains of the N-formyl peptide receptor are required for high-affinity ligand binding. J Biol Chem 1993; 288: 18167–18175.Google Scholar
  78. 78.
    Bahou WF, Coller BS, Potter CL, Norton KJ, Kutok JL, Goligorsky MS, The thrombin receptor extracellular domain contains sites crucial for peptide ligand-induced activation. J Clin Invest 1993; 91: 1405–1413.PubMedCrossRefGoogle Scholar
  79. 79.
    Zimmer Y, Givol D, Yayon A, Multiple structural elements determine ligand binding of fibroblast growth factor receptors: evidence that both Ig domain 2 and 3 define receptor specificity. J Biol Chem 1993; 268: 7899–7903.PubMedGoogle Scholar
  80. 80.
    Gayle RB, Sleath PR, Srinivason S, Birks CW, Weerawarna KS, Cerretti DP, Kozlosky CJ, Nelson N, Bos TV, Beckmann MP, Importance of amino terminus of the interleukin-8 receptor in ligand interactions. J Biol Chem 1993; 268: 7283–7289.PubMedGoogle Scholar
  81. 81.
    Juppner H, Schipani E, Bringhurst FR, McClure I, Keutmann HT, Potts JR, Kronenberg HM, Abou-Samra A.B., Segre GV, Gardella TJ. The extracellular amino-terminal region of the parathryoid hormone (PTH)/PTH-related peptide receptor determines the binding affinity for carboxyl-terminal fragments of PTH-O-34). Endocrinology 1994; 134: 879–884.PubMedCrossRefGoogle Scholar
  82. 82.
    Hjorth SA, Schambye HT, Greenlee WJ, Schwartz TW. Peptide binding residues in the extracellular domain of the AT1 receptor. Soc Neurosci Abs 1994;19:20.6.(Abstract)Google Scholar
  83. 83.
    Kubo T, Bujo H, Akiba I, Tunichi N, Mishima M, Numa S, Location of a region of the muscarinic acetylcholine receptor involved in selective effector coupling. FEBS Lett 1988; 241: 119–125.PubMedCrossRefGoogle Scholar
  84. 84.
    O’Dowd BF, Hnatowich M, Regan JW, Leader WM, Caron MG, Lefkowitz RJ, Site-directed mutagenesis of the cytoplasmic domains of the human beta-2-adrenergic receptor: Localization of regions involved in G protein-receptor coupling. J Biol Chem 1988; 263: 15985–15992.PubMedGoogle Scholar
  85. 85.
    Wang C-D, Buck MA, Fraser CM, Site directed mutagenesis of alpha-2A-adrenergic receptors: Identification of amino acids involved in ligand binding and receptor activation by agonists. Mol Pharmacol 1991; 40: 168–179.PubMedGoogle Scholar
  86. 86.
    Ohyama K, Yamano Y, Chaki S, Kondo T, Inagami T. Domains for G-protein coupling in angiotensin II receptor type I: Studies by site-directed mutagenesis. Biochem Biophys Res Commun 1992; 189: 677–683.PubMedCrossRefGoogle Scholar
  87. 87.
    Bihoreau C, Monnot C, Davies E, Teutsch B, Bernstein KE, Corvol P, Clauser E, Mutation of Asp74 of the rat angiotensin II receptor confers changes in antagonist affinities and abolishes G-protein coupling. Proc Natl Acad Sci USA 1993; 90: 5133–5137.PubMedCrossRefGoogle Scholar
  88. 88.
    Marie J, Maigret B, Joseph M-P, Larguier R, Nouet S, Lombard C, Bonnafous J-C, Tyr292 in the seventh transmembrane domain of the AT1a angiotensin II receptor is essential for its coupling to phospholipase C. J Biol Chem 1994; 269: 20815–20818.PubMedGoogle Scholar
  89. 89.
    Benovic JL, Bouvier M, Caron MG, Lefkowitz RJ, Regulation of adenylyl cyclase-coupled beta-adrenergic receptors. Annu Rev Cell Biol 1988; 4: 405–428.PubMedCrossRefGoogle Scholar
  90. 90.
    Bouvier M, Guilbault N, Bonin H, Phorbol-ester-induced phosphorylation of the beta-2-adrenergic receptor decreases its coupling to Gs. FEBS Lett 1991; 279: 243–248.PubMedCrossRefGoogle Scholar
  91. 91.
    Hausdorff WP, Campbell PT, Ostrowski J, Yu SS, Caron MG, Lefkowitz RJ, A small region of the beta-adrenergic receptor is selectively involved in its rapid regulation. Proc Natl Acad Sci U S A 1991; 88: 2979–2983.PubMedCrossRefGoogle Scholar
  92. 92.
    Kobilka B, Adrenergic receptors as models for G protein coupled receptors. Annu Rev Neurosci 1992; 15: 87–114.PubMedCrossRefGoogle Scholar
  93. 93.
    Yu SS, Lefkowitz RJ, Hausdorff WP, Beta-adrenergic receptor sequestration: A potential mechanism of receptor resensitization. J Biol Chem 1993; 268: 337–341.PubMedGoogle Scholar
  94. 94.
    Lee NH, Fraser CM, Cross-talk between ml muscarinic acetylcholine and beta-2-adrenergic receptors: cAMP and the third intracellular loop of ml muscarinic receptors confer heterologous regulation. J Biol Chem 1993; 268: 7949–7957.PubMedGoogle Scholar
  95. 95.
    Nakajima M, Mukoyama M, Pratt RE, Horiuchi M, Dzau VJ. Cloning of cDNA and analysis of the gene for mouse angiotensin-II type-2 receptor. Biochem Biophys Res Commun 1994; 197: 393–399.CrossRefGoogle Scholar
  96. 96.
    Ichiki T, Herold CL, Kambayashi Y, Bardhan S, Inagami T. Cloning of the cDNA and the genomic DNA of the mouse angiotensin II type 2 receptor. Biochim Biophys Acta 1994; 1189: 247–250.PubMedCrossRefGoogle Scholar
  97. 97.
    Moro O, Lameh J, Hogger P, Sadee W, Hydrophobie amino acid in the i2 loop plays a key role in receptor-G protein coupling. J Biol Chem 1993; 268: 22273–22276.PubMedGoogle Scholar
  98. 98.
    Fraser CM, Chung F-Z, Wang C-D, Venter JC, Site directed mutagenesis of human beta-adrenergic receptors: Substitution of aspartic acid-130 by asparagine produces a receptor with high-affinity agonist binding that is uncoupled from adenylate cyclase. Proc Natl Acad Sci U S A 1988; 85: 5478–5482.PubMedCrossRefGoogle Scholar
  99. 99.
    Fraser CM, Wang C-D, Robinson DA, Gocayne JD, Venter JC, Site-directed mutagenesis of ml muscarinicacetylcholine receptors: Conserved aspartic acids play important roles in receptor function. Mol Pharmacol 1989; 36: 840–847.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Steven J. Fluharty
    • 1
  • Lawrence P. Reagan
    • 1
  • Daniel K. Yee
    • 1
  1. 1.Departments of Animal Biology and Pharmacology and Institute of Neurological SciencesUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations