Cell Receptors pp 117-139 | Cite as

Molecular Biology of Receptors for Neuropeptide Hormones

  • D. Richter
  • W. Meyerhof
  • F. Buck
  • S. D. Morley
Part of the Current Topics in Pathology book series (CT PATHOLOGY, volume 83)


The theoretical concept of cell membrane-associated molecules which act as specific “receptors” for ligands such as peptide hormones, neurotransmitters, and various growth factors is long established. However, it is only in the last 8–10 years that convincing evidence has emerged for the functional role of these receptor proteins in the transduction of external stimuli into intracellular signals.


Adenylate Cyclase Brain Natriuretic Peptide Atrial Natriuretic Peptide Xenopus Oocyte Guanylate Cyclase 
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  1. Aoshima H, Iio H, Anan M, Ishii H, Kobayashi S (1987) Induction of muscarinic acetylcholine, serotonin and substance P receptors in Xenopus oocytes injected with mRNA prepared from the small intestine of rats. Mol Brain Res 2:15–20CrossRefGoogle Scholar
  2. Attramadal H, Eikvar L, Hansson V (1988) Mechanisms of glucagon-induced homologous and heterologous desensitization of adenylate cyclase in membranes and whole Sertoli cells of the rat. Endocrinology 123:1060–1068PubMedCrossRefGoogle Scholar
  3. Barish ME (1983) A transient calcium-dependent chloride current in the immature Xenopus oocyte. J Physiol 342:309–325PubMedGoogle Scholar
  4. Barnard EA, Beeson D, Bilbe G et al. (1983) Acetylcholine and GABA receptors: subunits of central and peripheral receptors and their encoding nucleic acids. CSH Symp on Quant Biology, The Cold Spring Harbor Laboratory, Cold Spring Harbor, vol XLVIII, pp 109–124Google Scholar
  5. Baxter JD, Lewicki JA, Gardner DG (1988) Atrial natriuretic peptide. Biotechnology 6:529–546CrossRefGoogle Scholar
  6. Benovic JL, Pike LJ, Cerione RA et al. (1985) Phosphorylation of the mammalian β-adrenergic receptor by cyclic AMP-dependent protein kinase. J Biol Chem 260:7094–7101PubMedGoogle Scholar
  7. Benovic JL, Strasser RH, Caron MG, Lefkowitz RJ (1986) β-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor. Proc Natl Acad Sci USA 83:2797–2801PubMedCrossRefGoogle Scholar
  8. Berridge MJ (1985) Inositol trisphosphate and diacylglycerol as intracellular second messengers. In: Poste G, Crooke ST (eds) Mechanisms of receptor regulation. Plenum Press, New York, pp 111–130CrossRefGoogle Scholar
  9. Berridge MJ (1987) Inositol trisphosphate and diacylglycerol: two interacting second messengers. Annu Rev Biochem 56:159–193PubMedCrossRefGoogle Scholar
  10. Berridge MJ, Irvine RF (1984) Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312:315–321PubMedCrossRefGoogle Scholar
  11. Biffen M, Martin BR (1987) Polyphosphoinositide labeling in rat liver plasma membranes is reduced by preincubation with cholera toxin. J Biol Chem 262:7744–7750PubMedGoogle Scholar
  12. Bokoch GM, Parkos CA, Mumby SM (1988) Purification and characterization of the 22000-dalton GTP-binding protein substrate for ADP-ribosylation by botulinum toxin, G22K. J Biol Chem 263:16744–16749PubMedGoogle Scholar
  13. Bouvier M, Leeb-Lundberg LMF, Benovic JL, Caron MG, Lefkowitz RJ (1987) Regulation of adrenergic receptor function by phosphorylation. J Biol Chem 262:3106–3113PubMedGoogle Scholar
  14. Bunzow JR, van Toi HHM, Grandy DK, Albert P, Salon J, Christie M, Machida CA, Neve KA, Civelli O (1988) Cloning, expression of a rat D2 dopamine receptor cDNA. Nature 336:783–787PubMedCrossRefGoogle Scholar
  15. Casey PJ, Gilman AG (1988) G protein involvement in receptor-effector coupling. J Biol Chem 263:2577–2580PubMedGoogle Scholar
  16. Cepko CL, Roberts BE, Mulligan RC (1984) Construction and applications of a highly transmissible murine retrovirus shuttle vector. Cell 37:1053–1062PubMedCrossRefGoogle Scholar
  17. Chang M-S, Lowe DG, Lewis M, Hellmiss R, Chen E, Goeddel DV (1989) Differential activation by atrial and brain natriuretic peptides of two different receptor guanylate cyclases. Nature 341:68–72PubMedCrossRefGoogle Scholar
  18. Chinkers M, Garbers DL, Chang M-S, Lowe DG, Chin H, Goeddel DV, Schulz S (1989) A membrane form of guanylate cyclase is an atrial natriuretic peptide receptor. Nature 338:78–83PubMedCrossRefGoogle Scholar
  19. Cockcroft S, Gomperts BD (1985) Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase. Nature 314:534–536PubMedCrossRefGoogle Scholar
  20. Colman A (1984) Translation of eukaryotic messenger RNA in Xenopus oocytes. In: Harnes BD, Higgins SJ (eds) Transcription and translation, a practical approach. IRL, Oxford, pp 271–302Google Scholar
  21. Creba JA, Downes CP, Hawkins PT, Brewster G, Micheli RH, Kirk CJ (1983) Rapid breakdown of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-biphosphate in rat hepatocytes stimulated by vasopressin and other Ca2+-mobilizing hormones. Biochem J 212:733–747PubMedGoogle Scholar
  22. Dickey BF, Pyun AY, Williamson KC, Navarro J (1987) Identification and purification of a novel G protein from neutrophils. FEBS Lett 219:289–292PubMedCrossRefGoogle Scholar
  23. Dixon RAF, Kobilka BK, Strader DJ et al. (1986) Cloning of the gene and cDNA for mammalian β-adrenergic receptor and homology with rhodopsin. Nature 321:75–79PubMedCrossRefGoogle Scholar
  24. Dohlman HG, Caron MG, Lefkowitz RJ (1987) A family of receptors coupled to guanine nucleotide regulatory proteins. Biochemistry 26:2657–2664PubMedCrossRefGoogle Scholar
  25. Eidne KA, McNiven AI, Taylor PL, Plant S, House CR, Lincoln DW, Yoshida S (1988) Functional expression of rat pituitary gonadotrophin-releasing hormone receptors in Xenopus oocytes. J MolEndocr 1:R9–R12Google Scholar
  26. Fahrenholz F, Boer F, Crause P, Toth MV (1985) Photoaffmity labelling of the renal V2 vasopressin receptor. Identification and enrichment of a vasopressin-binding subunit. Eur J Biochem 152:589–595PubMedCrossRefGoogle Scholar
  27. Fargin A, Raymond JR, Lohse MJ, Kobilka BK, Caron MG, Lefkowitz RJ (1988) The genomic clone G-21 which resembles a β-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature 335:358–360PubMedCrossRefGoogle Scholar
  28. Findlay J, Pappin DJC (1986) The opsin family of proteins. Biochem J 238:625–642PubMedGoogle Scholar
  29. Fitzgerald TJ, Uhing RJ, Exton JH (1986) Solubilization of the vasopressin receptor from rat liver plasma membranes. J Biol Chem 261:16871–16877PubMedGoogle Scholar
  30. Flynn TG, Davis PL (1985) The biochemistry and molecular biology of atrial natriuretic factor. Biochem J 232:313–321PubMedGoogle Scholar
  31. Fong HKW, Yoshimoto KK, Eversole-Cire P, Simon MI (1988) Identification of a GTP-binding protein a subunit that lacks an apparent ADP-ribosylation site for pertussis toxin. Proc Natl Acad Sci USA 85:3066–3070PubMedCrossRefGoogle Scholar
  32. Fuller F, Porter JG, Arfsten AE et al. (1988) Atrial natriuretic peptide clearance receptor. Complete sequence and functional expression of cDNA clones. J Biol Chem 263:9395–9401PubMedGoogle Scholar
  33. Garbers DL (1989) Guanylate cyclase, a cell surface receptor. J Biol Chem 264:9103–9106PubMedGoogle Scholar
  34. Gierschik P, Jacobs KH (1987) Receptor-mediated ADP-ribosylation of a phospholipase C-stimulating G protein. FEBS Lett 224:219–223PubMedCrossRefGoogle Scholar
  35. Gilbert W (1985) Genes-in-pieces revisited. Science 228:823–824PubMedCrossRefGoogle Scholar
  36. Gillo B, Lass Y, Nadler E, Oron Y (1987) The involvement of inositol 1,4,5-triphosphate and calcium in the two component response to acetylcholine in Xenopus oocytes. J Physiol 392:349–361PubMedGoogle Scholar
  37. Gilman AG (1987) G proteins: transducers of receptor-generated signals. Ann Rev Biochem 56:615–649PubMedCrossRefGoogle Scholar
  38. Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450PubMedGoogle Scholar
  39. Gurdon JB, Lane CD, Woodland HR, Marbaix G (1971) Use of frog eggs and oocytes for the study of messenger RNA and its translation in living cells. Nature 233:177–182PubMedCrossRefGoogle Scholar
  40. Harada Y, Takahashi T, Kuno M, Nakayama K, Masu Y, Nakanishi S (1987) Expression of two different tachykinin receptors in Xenopus oocytes by exogenous mRNAs. J Neurosci 7:3265–3273PubMedGoogle Scholar
  41. Hirono C, Ito J, Sugiyama H (1987) Neurotensin and acetylcholine evoke common responses in frog oocytes injected with rat brain messenger ribonucleic acid. J Physiol 382:523–535PubMedGoogle Scholar
  42. Iyengart R, Rich KA, Herberg JT, Grenet D, Mumby S, Codina J (1987) Identification of a new GTP-binding protein. J Biol Chem 262:9239–9245Google Scholar
  43. Jackson TR, Blair LAC, Marshall M, Goedert M, Hanley MR (1988) The mas oncogene encodes an angiotensin receptor. Nature 335:437–440PubMedCrossRefGoogle Scholar
  44. Julius D, MacDermott AB, Axel R, Jessell T (1988) Molecular characterization of a functional cDNA encoding the serotonin lc receptor. Science 241:558–564PubMedCrossRefGoogle Scholar
  45. Katada T, Oinuma M, Kusakabe K, Ui M (1987) A new GTP-binding protein in brain tissues serving as the specific substrate of islet-activating protein, pertussis toxin. FEBS Lett 213:353–358PubMedCrossRefGoogle Scholar
  46. Kline D, Simoncini L, Mandel G, Maue RA, Kado RT, Jaffe LA (1988) Fertilization events induced by neurotransmitters after injection of mRNA in Xenopus eggs. Science 241:464–467PubMedCrossRefGoogle Scholar
  47. Kobilka BK, Frielle T, Dohlman H et al. (1987) Delineation of the intronless nature of the genes for the human and hamster β2-adrenergic receptor and their putative promoter regions. J Biol Chem 262:7321–7327PubMedGoogle Scholar
  48. Kobilka BK, Kobilka TS, Daniel K, Regen JW, Caron MG, Lefkowitz RJ (1988) Chimeric α2-, β2-adrenergic receptors: delineation of domains involved in effector coupling and ligand binding specificity. Science 248:1310–1316CrossRefGoogle Scholar
  49. Krieger D (1983) Brain peptides: What, where and why? Science 222:975–985PubMedCrossRefGoogle Scholar
  50. Kusano K, Miledi R, Stinnakre J (1977) Acetylcholine receptors in the oocyte membrane. Nature 270:739–741PubMedCrossRefGoogle Scholar
  51. Lefkowitz RJ, Caron MG (1988) Adrenergic receptors. J Biol Chem 263:4993–4996PubMedGoogle Scholar
  52. Libert F, Parmentier M, Lefort A et al. (1989) Selective amplification and cloning of four new members of the G protein-coupled receptor family. Science 244:569–572PubMedCrossRefGoogle Scholar
  53. Litosch I, Wallis C, Fain JN (1985) 5-hydroxytryptamine stimulates inositol phosphate production in a cell-free system from blowfly salivary glands. J Biol Chem 260:5464–5471PubMedGoogle Scholar
  54. Lo WWY, Hughes J (1987) Receptor-phosphoinositidase C coupling. FEBS Lett 224:1–3PubMedCrossRefGoogle Scholar
  55. Lochrie MA, Simon MI (1988) G protein multiplicity in eukaryotic signal transduction systems. Biochemistry 27:4957–4965PubMedCrossRefGoogle Scholar
  56. Lowe DG, Chang M-S, Hellmiss R, Chen E, Singh S, Garbers DL, Goeddel DV (1989) Human atrial natriuretic peptide receptor defines a new paradigm for second messenger signal transduction. EMBO J 8:1377–1384PubMedGoogle Scholar
  57. Machida CA, Bunzow J, Hanneman E, Grandy D, Civelli O (1989) Replica filter screening technique to detect transfected cells expressing β2-adrenergic receptor. DNA 8:447–455PubMedCrossRefGoogle Scholar
  58. Maelicke A (1989) Cloning of a rat D2-dopamine receptor. Trends Biochem Sci 14:41–42PubMedCrossRefGoogle Scholar
  59. Mahlmann S, Meyerhof W, Schwarz JR (1989 a) Different roles of IP4 and IP3 in the signal pathway coupled to the TRH receptor in microinjected Xenopus oocytes. FEBS Lett 249:108–112CrossRefGoogle Scholar
  60. Mahlmann S, Schwarz JR, Meyerhof W (1989 b) Modulation of neuropeptide-induced membrane currents by protein kinase C in Xenopus oocytes injected with GH3 pituitary cell poly(A) + RNA. J Neuroendocrinol 1:65–69PubMedCrossRefGoogle Scholar
  61. Marx JL (1988) Multiplying genes by leaps and bounds. Science 240:1408–1410PubMedCrossRefGoogle Scholar
  62. Masu Y, Nakayama K, Tamaki H, Harada Y, Motoy K, Nakanishi S (1987) cDNA cloning of bovine substance-K receptor through oocyte expression system. Nature 329:836–838PubMedCrossRefGoogle Scholar
  63. Mcintosh RP, Catt KJ (1987) Coupling of inositol phospholipid hydrolysis to peptide hormone receptors expressed from adrenal and pituitary mRNA in Xenopus laevis oocytes. Proc Natl Acad Sci USA 84:9045–9048PubMedCrossRefGoogle Scholar
  64. Methfessel C, Witzemann V, Takahashi T, Mishina M, Numa S, Sakmann B (1986) Patch clamp measurements on Xenopus laevis oocytes: currents through endogenous channels and implanted acetylcholine receptor and sodium channels. Pflugers Arch 407:577–588PubMedCrossRefGoogle Scholar
  65. Meyerhof W, Richter D (1989) Characterization of neuropeptide-induced membrane chloride currents in Xenopus oocytes primed with exogenous mRNA. J Protein Chem 8:365–368PubMedCrossRefGoogle Scholar
  66. Meyerhof W, Morley S, Schwarz J, Richter D (1988 a) Receptors for neuropeptides are induced by exogenous poly(A)+ RNA in oocytes from Xenopus laevis. Proc Natl Acad Sci USA 85:714–717PubMedCrossRefGoogle Scholar
  67. Meyerhof W, Morley SD, Richter D (1988 b) Expression and electrophysiological identification of the receptor for bombesin and gastrin-releasing peptide in Xenopus laevis oocytes injected with polyA + RNA from rat brain. FEBS Lett 239:109–112PubMedCrossRefGoogle Scholar
  68. Miledi R (1982) A calcium-dependent transient outward current in Xenopus laevis oocytes. Proc R Soc Lond [Biol] 215:491–497CrossRefGoogle Scholar
  69. Minamino N, Aburaya M, Ueda S, Kangawa K, Matsuo H (1988) The presence of brain natriuretic peptide of 12000 daltons in porcine heart. Biochem Biophys Res Commun 155:740–746PubMedCrossRefGoogle Scholar
  70. Moriarty TM, Gillo B, Sealfon S, Roberts JL, Blitzer RD, Landau EM (1988) Functional expression of brain cholecystokinin and bombesin receptors in Xenopus oocytes. Mol Brain Res 4:75–79CrossRefGoogle Scholar
  71. Morley SD, Meyerhof W, Schwarz J, Richter D (1988) Functional expression of the oxytocin receptor in Xenopus laevis oocytes primed with mRNA from bovine endometrium. J Mol Endocrinol 1:77–81PubMedCrossRefGoogle Scholar
  72. Noma Y, Sideras P, Naito T et al. (1986) Cloning of a cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter. Nature 319:640–646PubMedCrossRefGoogle Scholar
  73. Northup JK (1985) Overview of the guanine nucleotide regulatory protein systems, Ns and Ni, which regulate adenylate cyclase activity in plasma membranes. In: Cohen P, Housley MD (eds) Molecular mechanisms of transmembrane signalling. Elsevier, Amsterdam, pp 91–116Google Scholar
  74. O’Dowd BF, Hnatowich M, Caron MG, Lefkowitz RJ, Bouvier M (1989) Palmitoylation of the human β2-adrenergic receptor. J Biol Chem 264:7564–7569PubMedGoogle Scholar
  75. Oron Y, Dascal N, Nadler E, Lupu M (1985) Inositol 1,4,5-trisphosphate mimics muscarinic response in Xenopus oocytes. Nature 313:141–143PubMedCrossRefGoogle Scholar
  76. Oron Y, Gillo B, Straub RE, Gershengorn MC (1987) Mechanism of membrane electrical response to thyrotropin-releasing hormone in Xenopus oocytes injected with GH3 pituitary cell messenger ribonucleic acid. Mol Endocrinol 1:918–925PubMedCrossRefGoogle Scholar
  77. Parker I, Miledi R (1986) Changes in intracellular calcium and in membrane currents evoked by injection of inositol trisphosphate into Xenopus oocytes. Proc R Soc Lond [Biol] 228:307–315CrossRefGoogle Scholar
  78. Parker I, Sumikawa K, Miledi R (1986) Neurotensin and substance P receptors expressed in Xenopus oocytes by messenger RNA from rat brain. Proc R Soc Lond [Biol] 229:151–159CrossRefGoogle Scholar
  79. Parker I, Sumikawa K, Miledi R (1987) Activation of a common effector system by different brain neurotransmitter receptors in Xenopus oocytes. Proc R Soc Lond [Biol] 231:37–45CrossRefGoogle Scholar
  80. Perucho M, Hanahan D, Wigler M (1980) Genetic and physical linkage of exogenous sequences in transformed cells. Cell 22:309–317PubMedCrossRefGoogle Scholar
  81. Richter D (1988) Molecular events in expression of vasopressin and oxytocin and their cognate receptors. Am J Physiol 255:F207–F219PubMedGoogle Scholar
  82. Richter D, Morley SD, Schwarz J, Meyerhof W (1988 a) Characterising neuropeptide signaling pathways. In: Thorn NA, Treiman M, Petersen OH (eds) Molecular mechanisms in secretion. Alfred Benzon Symposium 25. Munksgaard, Copenhagen, pp 544–553Google Scholar
  83. Richter D, Meyerhof W, Morley SD, Mohr E, Fehr S, Schmale H (1988 b) Molecular biology of brain peptides and their cognate receptors. In: Kleinkauf, von Döhren, Jaenicke (eds) The roots of modern biochemistry. Walter de Gruyter, Berlin, pp 305–321CrossRefGoogle Scholar
  84. Ross EM (1989) Signal sorting and amplification through G protein-coupled receptors. Neuron 3:141–152PubMedCrossRefGoogle Scholar
  85. Saiki RK, Gelfand DH, Stoffel S et al. (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491PubMedCrossRefGoogle Scholar
  86. Sandberg K, Markwick AJ, Trinh DP, Catt KJ (1988) Calcium mobilization by angiotensin II and neurotransmitter receptors expressed in Xenopus laevis oocytes. FEBS Lett 241:177–180PubMedCrossRefGoogle Scholar
  87. Sibley DR, Nambi P, Lefkowitz RJ (1985) Molecular mechanisms of hormone receptor desensitization. In: Cohen P, Houslay MD (eds) Molecular mechanisms of transmembrane signalling. Elsevier, Amsterdam, pp 359–374Google Scholar
  88. Sibley DR, Benovic JL, Caron MG, Lefkowitz RJ (1987) Regulation of transmembrane signaling by receptor phosphorylation. Cell 48:913–922PubMedCrossRefGoogle Scholar
  89. Singh S, Lowe DG, Thorpe DS et al. (1988) Membrane guanylate cyclase is a cell-surface receptor with homology to protein kinases. Nature 334:708–712PubMedCrossRefGoogle Scholar
  90. Sternweis PC, Robishaw JD (1984) Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain. J Biol Chem 259:13806–13813PubMedGoogle Scholar
  91. Sudoh T, Kangawa K, Minamino N, Matsuo H (1988) A new natriuretic peptide in porcine brain. Nature 332:78–81PubMedCrossRefGoogle Scholar
  92. Waldo GL, Evans T, Fraser ED, Northup JK, Martin MW, Harden TK (1987) Identification and purification from bovine brain of a guanine-nucleotide-binding protein distinct from Gs, Gi and G0. Biochem J 246:431–439PubMedGoogle Scholar
  93. Williams JA, McChesney DJ, Calayag MC, Lingappa VR, Logsdon CD (1988) Expression of receptors for cholecystokinin and other Ca2+ mobilizing hormones in Xenopus oocytes. Proc Natl Acad Sci USA 85:4939–4943PubMedCrossRefGoogle Scholar
  94. Yarden Y, Ullrich A (1988) Molecular analysis of signal transduction by growth factors. Biochemistry 27:3113–3119PubMedCrossRefGoogle Scholar
  95. Young D, Waitches G, Birchmeier C, Fasano O, Wigler M (1986) Isolation and characterization of a new cellular oncogene encoding a protein with multiple potential transmembrane domains. Cell 45:711–719PubMedCrossRefGoogle Scholar
  96. Young D, O’Neill K, Jessell T, Wigler M (1988) Characterization of the rat mas oncogene and its high-level expression in the hippocampus and cerebral cortex of rat brain. Proc Natl Acad Sci USA 85:5339–5342PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • D. Richter
  • W. Meyerhof
  • F. Buck
  • S. D. Morley

There are no affiliations available

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