Vasopressin pp 175-209 | Cite as

Biosynthesis of Vasopressin and Neurophysins

  • William G. North


Vasopressin (VP) is a product of magnocellular neurons in the anterior hypothalamus, most of which have axons that terminate in the neural lobe. The VP gene is also probably expressed by neurons in other brain loci (Caffe and Van Leeuwen, 1983; Sofroniew, 1983; Caffe et al., 1985), and by cells outside the central nervous system (CNS) (Lim et al., 1984; Nussey et al., 1984), but it has yet to be established that VP itself is the final secreted product of this expression. In hypothalamic neurons, VP is translated as a preprohormone that loses an N-ter-minal signal peptide and undergoes final glycosylation in the Golgi apparatus to form a prohormone. This prohormone is packaged into neurosecretory vesicles (NSV); during transport within these vesicles to axonal terminals, it is acted on by intravesicular enzymes that generate the active nonapeptide amide, a 10,000-M r protein called neurophysin, and a 39-amino acid glycopeptide. All three products are released into the peripheral circulation and have been immunologically identified in plasma (North et al., 1983a; Groesbeck et al., 1983). The nomenclature preproVP and pro VP is used in this text to denote preprohormone and prohormone. Distinct neurons in the hypothalamus produce oxytocin (OX), a peptide that is chemically and structurally similar to VP. In fact, it is highly likely that the OX and the VP genes are derived from a common ancestral gene—that VP and OX neurons share a common ancestral neuron (Sawyer, 1977). Therefore, not surprisingly, OX was found to be first translated as a preprohormone (prepro-oxytocin); this converted to a prohormone (pro-oxytocin). Pro-oxytocin undergoes enzymatic modification in the NSV of OX neurons to form oxytocin and a neurophysin (NP). However, through what is currently believed to have arisen as a base deletion or a base insertion in the OX gene, pro-oxytocin does not contain a moiety that will become a glycopeptide (Ivell and Richter, 1984). Since the neu-rophysins produced with each hormone are distinct molecules, they have been named vasopressin-associated neurophysin (VP-NP) and oxytocin-associated neurophysin (OX-NP) (North et al., 1911a).


Hypothalamic Neuron Supraoptic Nucleus Neural Lobe Neurohypophysial Hormone Carbohydrate Side Chain 
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. Bargmann, W., and Gaudecker, B. V., 1969, Uber die Ultrastrukture neurosekretorischer Elementar-granular, Z. Zellforsch. Microsk. Anat. 96: 495–504.Google Scholar
  2. Berde, B., and Boissonnas, R. A., 1968, Basic pharmacological properties of synthetic analogues and homologues of the neurohypophysial hormones, in: Handbook of Experimental Pharmacology, Vol. 23 (B. Berde, ed.), pp. 802–870, Springer-Verlag, Berlin.Google Scholar
  3. Bettinger, G. E., and Young, E. F., 1975, Tunicamycin, an inhibitor of Barillas peptidoglycan synthesis: A new site of inhibition, Biochem. Biophys. Res. Commun. 67: 16–21.PubMedGoogle Scholar
  4. Birkett, S. D., Swann, R. W., Gonzalez, C. B., and Pickering, B. T., 1983, Analysis of the neurohy-pophyseal components accumulating in the supraoptic nucleus of the rat after injection of col-chicine, Arch. Biochem. Biophys. 225: 430–435.PubMedGoogle Scholar
  5. Bradbury, A. F., Finnie, M. D. A., and Smyth, D. G., 1982, Mechanism of C-terminal amide formation by pituitary enzymes, Nature (Lond.) 298: 686–688.Google Scholar
  6. Breslow, E., 1979, Chemistry and biology of the neurophysins, Annu. Rev. Biochem. 48: 251–274.PubMedGoogle Scholar
  7. Breslow, E., Pagnozzi, M., and Tiao-te Co, R., 1982, Chemical modification or excision of neurophy-sin arginine-8 is associated with loss of peptide-binding ability, Biochem. Biophys. Res. Commun. 106: 194–201.PubMedGoogle Scholar
  8. Brownstein, M. J., and Gainer, H., 1977a, Neurophysin biosynthesis in normal rats and in rats with hereditary diabetes insipidus, Proc. Natl. Acad. Sci. U.S.A. 74: 4046–4049.PubMedGoogle Scholar
  9. Brownstein, M. J., Robinson, A. G., and Gainer, H., 1977b, Immunological identification of rat neurophysin precursor, Nature (Lond.) 269: 259–261.Google Scholar
  10. Brownstein, M. J., Russell, J. T., and Gainer, H., 1979, Synthesis, transport, and release of posterior pituitary hormones, Science 207: 373–378.Google Scholar
  11. Buijs, R. M., and Van Heerikhuize, J. J., 1982, Vasopressin and oxytocin release in the brain—A synaptic event, Brain Res. 252: 71–76.PubMedGoogle Scholar
  12. Burbach, J. P. H., and Lebouille, J. L. M., 1983, Proteolytic conversion of arginine-vasopressin and oxytocin by brain synaptic membranes, J. Biol. Chem. 258: 1487–1494.PubMedGoogle Scholar
  13. Burbach, J. P. H., Kovacs, G. L., De Wied, D., Van Nispen, J. W., and Greven, H. M., 1983a, A major metabolite of arginine-vasopressin in the brain is a highly potent neuropeptide, Science 221: 1310–1312.PubMedGoogle Scholar
  14. Burbach, J. P. H., Wang, X.-C, and van Ittersum, M., 1983b, Difference in susceptibility of arginine-vasopressin and oxytocin to aminopeptidase activity in brain synaptic membranes, Biochem. Biophys. Res. Commun. 108: 1165–1171.Google Scholar
  15. Burbach, J. P. H., Wang, X.-C., Ten Haaf, J. A., and De Wied, D., 1984, Substances resembling C-terminal vasopressin fragments are present in the brain but not in the pituitary gland, Brain Res. 306: 384–387.PubMedGoogle Scholar
  16. Burbach, J. P. H., De Hoop, M. J., Schmale, H., Richter, D., De Kloet, E. R., Ten Haaf, J. A., and De Wied, D., 1984, Differential responses to osmotic stress of vasopressin-neurophysin mRNA in hypothalamic nuclei, Neuroendocrinology 39: 582–584.PubMedGoogle Scholar
  17. Burford, G. D., and Pickering, B. T., 1973, Intra-axonal transport and turnover of neurophysins in the rat. A proposal for a possible origin of the minor neurophysin component, Biochem. J. 136: 1047–1052.PubMedGoogle Scholar
  18. Caffe, A. R., and Van Leeuwen, F. W., 1983, Vasopressin-immunoreactive cells in the dorsomedial hypothalamic region, medial amygdaloid nucleus and locus coeruleus of the rat, Cell Tissue Res. 233: 23–33.PubMedGoogle Scholar
  19. Caffe, A. R., Van Leeuwen, F. W., Buijs, R. M., de Vries, G. J., and Geffard, M., 1985, Coexistence of vasopressin, neurophysin and noradrenaline immunoreactivity in medium-sized cells of the locus coeruleus and subcoeruleus in the rat, Brain Res. 338: 160–164.PubMedGoogle Scholar
  20. Carney, D. N., Gazdar, A. F., Oie, H. K., Herbert, K., Cuttitta, F., and Minna, J. D., 1983, The in vitro growth and characterization of small cell lung cancer, in: Biology and Management of Lung Cancer (F. A. Greco, ed.), pp. 1–24. Martinus Nijhoff, Boston.Google Scholar
  21. Chaiken, I. M. Abercrombie, D. M., Kanmera, T., and Sequeria, R. P., 1983, Neuronal peptide-protein complexes: Neurophysins and associated neuropeptide hormones, in: Peptide and Protein Reviews, vol. 1 (M. T. W. Hearn, ed.), pp. 139–209, Dekker, New York.Google Scholar
  22. Chauvet, M.-T., Cadogno, P., Chauvet, J., and Acher, R., 1977, Phylogeny of the neurophysins: Complete amino acid sequence of horse MSEL-neurophysin, FEBS Lett. 80: 374–376.PubMedGoogle Scholar
  23. Chauvet, M.-T., Chauvet, J., and Acher, R., 1981, Identification of rat neurophysins: Complete amino acid sequences of MSEL-and VLDV-neurophysins, Biochem. Biophys. Res. Commun. 103: 595–603.PubMedGoogle Scholar
  24. Chauvet, M.-T., Hurpet, D., Chauvet, J., and Acher, R., 1982, The neurophysin domain of human vasopressin precursor, FEBS Lett. 143: 183–187.PubMedGoogle Scholar
  25. Chauvet, J., Chauvet, M.-T., Hurpet, D., and Acher, R., 1984, Evolution of multidomain neuropep-tide precursors: Vertebrate neurohypophysial hormones and neurophysins, in: Seventh International Congress on Endocrinology, Canada. (Abst. 347.)Google Scholar
  26. Czichi, U., and North, W. G., 1985, Ectopic production and processing of provasopressin by small cell carcinoma of the lung, in: Proceedings of the National Meeting of the Endocrinology Society, Baltimore. (Abst. 963.)Google Scholar
  27. De Wied, D., 1983, Central actions of neurohypophysial hormones, Prog. Brain Res. 60: 155–168.PubMedGoogle Scholar
  28. Docherty, K., and Steiner, D., 1982, Post-translational proteolysis in polypeptide hormone biosynthesis, Annu. Rev. Physiol. 44: 625–638.PubMedGoogle Scholar
  29. du Vigneaud, V., Ressler, C., Swann, J. M., Katsoyannis, P. G., and Roberts, C. W., 1954a, Synthesis of oxytocin, J. Am. Chem. Soc. 76: 3115–3121.Google Scholar
  30. du Vigneaud, V., Gish, D. T., and Katsoyannis, P. G., 1954b, A synthetic preparation processing biological properties associated with arginine vasopressin, J. Am. Chem. Soc. 76: 4751–4752.Google Scholar
  31. Eipper, B. A., Mains, R. E., and Glembotski, C. C, 1983, Identification in pituitary tissue of a peptide α-amidation activity that acts on glycine-extended peptides requires molecular oxygen, copper, and ascorbic acid, Proc. Natl. Acad. Sci U.S.A. 80: 5144–5148.PubMedGoogle Scholar
  32. Fricker, L. D., and Snyder, S. H., 1982, Enkephalin convertase: Purification and characterization of a specific enkephalin-synthesizing carboxypeptidase localized to adrenal chromaffin vesicles, Proc. Natl. Acad. Sci. U.S.A. 79: 3886–3890.PubMedGoogle Scholar
  33. Flicker, L. D., and Snyder, S. H., 1983, Purification and characterization of enkephalin convertase, an enkephalin-synthesizing carboxypeptidase, J. Biol. Chem. 258: 10950–10955.Google Scholar
  34. Fuller, P. J., Clements, J. A., Tregear, G. W., Nikolaidis, I., Whitfield, P. L., and Funder, J. W., 1985, Vasopressin-neurophysin II gene expression in the ovary: Studies in Sprague-Dawley, Long-Evans and Brattleboro rats, J. Endocrinol. 105: 317–321.PubMedGoogle Scholar
  35. Gainer, H., Same, Y., and Brownstein, M. J., 1977, Biosynthesis and axonal transport of rat neurohypophysial proteins and peptides, J. Cell. Biol. 73: 366–381.Google Scholar
  36. Gainer, H., Russell, J. T., and Loh, Y. P., 1984, An amidopeptidase activity in bovine pituitary secretory vesicles that cleaves the N-terminal arginine from β-lipotropin 60–65 FEBS Lett. 175: 135–139.Google Scholar
  37. Gainer, H., Russell, J. T., and Loh, Y. P., 1985, The enzymology and intracellular organization of peptide precursor processing: The secretory vesicle hypophesis, Neuroendocrinology 40: 171–184.PubMedGoogle Scholar
  38. Gonzalez, C. B., 1983, Components in the biosynthetic pathway to neurohypophyseal hormones with special reference to glycosylation, Ph.D. thesis, University of Bristol.Google Scholar
  39. Greep, R. O., and Astwood, E. B., 1974, Handbook of Physiology. Endocrinology, Vol. IV: The Pituitary Gland and Its Neuroendocrine Control, Part 1, American Physiological Society, Washington, D.C.Google Scholar
  40. Groesbeck, M. D., Shome, B., and Parlow, A. F., 1983, The isolated carboxy terminal glycopeptide of rat vasopressin-neurophysin precursor, in: Proceedings of the National Endocrine Society. (Abst. 259.)Google Scholar
  41. Hamilton, B. P., Upton, G. V., and Amatruda, T. T., Jr., 1972, Evidence for the presence of neurophysin in tumors producing the syndrome of inappropriate antidiuresis, J. Clin. Endocrinol. 35: 764–767.Google Scholar
  42. Hirs, C. H. W., 1976, Specificity of chymotrypsin for hydrolysis of peptide bonds in proteins and polypeptides, in: Handbook of Biochemistry and Molecular Biology, Proteins, Vol. II, 3rd ed. (G. D. Fasman, ed.), pp. 212–213, CRC Press, Boca Raton, Florida.Google Scholar
  43. Holwerda, D. A., 1972, A glycopeptide from the posterior lobe of pig pituitaries. II. Primary structures, Eur. J. Biochem. 28: 340–346.PubMedGoogle Scholar
  44. Hook, V. Y. H., and Loh, Y. P., 1984, Carboxypeptidase β-like converting enzyme activity in secretory vesicles of rat pituitary, Proc. Natl. Acad. Sci. U.S.A. 81: 2777–2780.Google Scholar
  45. Hubbard, S. C., and Ivatt, R. J., 1981, Synthesis and processing of asparagine-linked oligosaccharides Annu. Rev. Biochem. 50: 555–583.PubMedGoogle Scholar
  46. Ivell, R., and Richter, D., 1984, Structure and comparison of the oxytocin and vasopressin genes from rat, Proc. Natl. Acad. Sci. U.S.A. 81: 2006–2010.PubMedGoogle Scholar
  47. Ivell, R., Schmale, H., and Richter, D., 1983, Vasopressin and oxytocin precursors as model prepro-hormones, Neuroendocrinology 37: 235–239.PubMedGoogle Scholar
  48. Ivell, R., Schmale, H., Krisch, B., Nahke, P., and Richter, D. 1986, Expression of a mutant vasopressin gene: Differential polyadenylation and read-through of the mRNA 3′-end in a frame-shift mutant, EMBO J. 5: 971–977.PubMedGoogle Scholar
  49. Jones, C. W., and Swann R. W., 1975, A glycoprotein in the neurosecretory vesicles of the neurohy-pophysis, J. Physiol. (Lond.) 245: 45P.Google Scholar
  50. Jones, P. M., Saermark, T., and Robinson, I.C.A.F., 1984, Conversion and release of an intermediate in vasopressin-neurophysin biosynthesis in the guinea-pig, J. Endocrinol. 103: 347–354.PubMedGoogle Scholar
  51. Kirsch, B., 1980, Nongranular vasopressin biosynthesis and transport, Cell Tissue Res. 207: 89–107.Google Scholar
  52. Land, H., Schutz, G., Schmale, H., and Richter, D., 1982, Nucleotide sequence of cloned cDNA encoding bovine arginine vasopressin-neurophysin II precursor, Nature (Lond.) 295: 299–303.Google Scholar
  53. Land, H., Grez, M., Ruppert, S., Schmale, H., Rehbein, M., Richter, D., and Schutz, G., 1983, Deduced amino acid sequence from the bovine oxytocin-neurophysin I precursor cDNA, Nature (Lond.) 302: 342–344.Google Scholar
  54. LaRochelle, F. T., Jr., North, W. G., and Stern, P., 1980, A new extraction of arginine vasopressin from blood: The use of octadecasilyl-silica, Pflugers Arch. Eur. J. Physiol. 387: 79–81.Google Scholar
  55. Lauber, M., Nicholas, P., Boussetta, H., Fahy, C., Beguin, P., Camier, M., Vaudry, H., and Cohen, P., 1981, The Mr 80,000 common forms of neurophysin and vasopressin from bovine neurohypo-physis have corticotrophin-and ′-endorphin-like sequences and liberate by proteolysis biologically active corticotrophin, Proc. Natl. Acad. Sci. U.S.A. 78: 6086–6090.PubMedGoogle Scholar
  56. Legros, J.-J., Louis, F., Grotschel-Stewart, U., and Franchimont, P., 1975, Presence of immunoreac-tive neurophysin-like material in human target organs and pineal gland: Physiological meaning, NY. Acad. Sci. 248: 157–171.Google Scholar
  57. Lewis, R. V., and Stern, A. S., 1983, Biosynthesis of the enkephalins and enkephalin-containing poly-peptides, Annu. Rev. Pharmacol. 23: 353–372.Google Scholar
  58. Lim, A. T. W., Lolait, S. J., Barlow, J. W., Autelitano, D. J., Toh, B. H., Boublik, J., Abraham, J., Johnston, C. I., and Funder, J. W., 1984, Immunoreactive arginine-vasopressin in Brattleboro rat ovary, Nature (Lond.) 310: 61–64.Google Scholar
  59. Livingston, A., and Lederis, K., 1971, Functional ultrastructure of the neurohypophysis, Mem. Soc. Endocrinol. 19: 233–262.Google Scholar
  60. Loh, Y. P., and Gainer, H., 1982, Characterization of pro-opiocortin-converting activity in purified secretory vesicles from rat pituitary neurointermediate lobe, Proc. Natl. Acad. Sci. U.S.A. 79: 108–112.Google Scholar
  61. Loh, Y. P., Parish, D. C., and Tuteja, R., 1984, Proteolytic processing of pro-opiomelanocortin by an unique LYS-ARG specific converting enzyme from bovine pars intermedia secretory vesicles, in: Endocrinology (F. Labrie and L. Proulx, eds.), pp. 393–396, Excerpta Medica, Amsterdam.Google Scholar
  62. Mains, R. E., Eipper, B. A., Glembotski, C. C., and Dores, R. M., 1983, Strategies for the biosynthesis of bioactive peptides, Trends Neurosci. 52: 229–235.Google Scholar
  63. Mains, R. E., Glembotski, C., and Eipper, B. A., 1984, Peptide α-amidation activity in mouse anterior pituitary At T-20 cell vesicles: Properties and secretion, Endocrinology 114: 1522–1530.PubMedGoogle Scholar
  64. Majzoub, J. A., 1985, Vasopressin biosynthesis, in: Vasopressin (R. W. Schrier, ed.) pp. 465–474, Raven, New York.Google Scholar
  65. Majzoub, J. A., Pappey, A., Burg, R., and Habener, J. F., 1984a, Vasopressin gene is expressed at low levels in the hypothalamus of the Brattleboro rat, Proc. Natl. Acad. Sci. U.S.A. 81: 5296–5299.PubMedGoogle Scholar
  66. Majzoub, J. A., Sokol, J., and Habener, J., 1984b, Vasopressin gene regulation in the rat hypothalamus, in: Seventh International Congress of Endocrinology. (Abst. 1293.)Google Scholar
  67. Manning, M., and Sawyer, W. H., 1977, Structure-activity studies on oxytocin and vasopressin 1954–1976: From empiricism to design, in: Conference on the Neurohypophysis (A. Moses and L. Share, eds.), pp. 9–21, Karger, Basel.Google Scholar
  68. Manning, M., and Sawyer, W. H., 1983, Design of potent and selective in vivo antagonists of the neurohypophysial peptides, Prog. Brain Res. 60: 367–382.PubMedGoogle Scholar
  69. Manning, M., Olma, A., Klis, W., Kolodziejczyk, A., Nawrocka, E., Misicka, A., Seto, J., and Sawyer, W. H., 1984, Carboxy terminus of vasopressin required for activity but not for binding, Nature (Lond.) 308: 652–653.Google Scholar
  70. Maurer, L. H., O’Donnell, J. F., Kennedy, S., Faulkner, C. S., Rist, K., and North, W. G., 1983, Human neurophysins in carcinoma of the lung: Relation to histology, disease stage, survival, and syndrome of inappropriate antidiuretic hormone secretion, Cancer Treatm. Rep. 67: 971–976.Google Scholar
  71. Mehmet, F. F., Grosh, W. W., and Greco, F. A., 1983, Morphologic changes in small cell lung cancer, in: Biology and Management of Lung Cancer (F. A. Greco, ed.), pp. 109–124, Martinus-Nijhoff, Boston.Google Scholar
  72. Mohr, E., Hillers, M., Ivell, R., Haulica, I. D., and Richter, D., 1985, Expression of the vasopressin and oxytocin genes in human hypothalami, FEBS Lett. 193: 12–16.PubMedGoogle Scholar
  73. Moore, G. J., Kwok, Y. C., Ko, E. M., Severson, D. L., and Rosenior, J. C., 1982, Extended chain analogs of [arginine8] vasopressin as model prohormones: Investigation of precursor-processing enzymes in extracts of the rat hypothalamus and neural lobe, Endocrinology 111: 1626–1631.PubMedGoogle Scholar
  74. Morris, J. F., and Cannata, M. A., 1973, Ultrastructural preservation of the dense core of posterior pituitary neurosecretory vesicles and its implications for hormone release, J. Endocrinol. 57: 517–529.PubMedGoogle Scholar
  75. Morris, J. F., 1976, Hormone storage in individual neurosecretory vesicles of the pituitary gland: A quantitative ultrastructural approach to hormone storage in the neural lobe, J. Endocrinol. 68: 209–224.PubMedGoogle Scholar
  76. Morris, J. F., Sokol, H. W., and Valtin, H., 1977, One neuron-one hormone? Recent evidence from Brattleboro rats, in: Neurohypophysis (A. M. Moses and L. Share, eds.), pp. 56–66, Karger, Basel.Google Scholar
  77. Morris, J. F., 1982, The Brattleboro magnocellular neurosecretory system: A model for the study of peptidergic neurons, Ann. N.Y. Acad. Sci. 394: 54–71.PubMedGoogle Scholar
  78. Morris, J. F., 1983, Organization of neural inputs to the supraoptic and paraventricular nuclei: Anatomical aspects, Prog. Brain Res. 60: 3–18.PubMedGoogle Scholar
  79. Nordmann, J. J., 1982, Evidence for an aging process within neurosecretory vesicles, in: Vasopressin, Corticoliberin and ACTH-related Peptides (A. J. Baartschi and J. J. Dreifus, eds.), pp. 11.-20, Academic, London.Google Scholar
  80. Nordmann, J. J., 1983, Stimulus-secretion coupling, Prog. Brain Res. 60: 281–304.Google Scholar
  81. North, W. G., 1983, Biosynthesis of vasopressin, in: Proceedings of the Thirty-Ninth International Congress of Physiological Science, Sydney, Australia.Google Scholar
  82. North, W. G., 1984, Processing of provasopressin: Identification of a carboxypeptidase associated with neurosecretory vesicles, in: Proceedings of the Seventh International Congress of Endocrinology. (Abst. 1568.)Google Scholar
  83. North, W. G., and Mitchell, T. I., 1981, Evolution of neurophysin proteins: The partial sequence of rat neurophysins, FEBS Lett. 126: 41–44.PubMedGoogle Scholar
  84. North, W. G., Walter, R., Schlesinger, D. H., Breslow, E., and Capra, L. D., 1975, Structural studies of bovine neurophysin-I, Ann. N.Y. Acad. Sci. 248: 408–422.PubMedGoogle Scholar
  85. North, W. G., Morris, J. F., LaRochelle, F. T., Jr., and Valtin, H., 1977a, Enzymatic interconversions of neurophysins, in: Neurohypophysis (A. M. Moses and L. Share, eds.), pp. 43–52, Karger, Basel.Google Scholar
  86. North, W. G., Valtin, H., Morris, J. F., and LaRochelle, F. T., Jr., 1977b, Evidence for metabolic conversions of rat neurophysins within neurosecretory vesicles of the hypothalamo-neurohypo-physial system, Endocrinology 101: 110–118.PubMedGoogle Scholar
  87. North, W. G., LaRochelle, F. T., Jr., Morris, Jr. R., Sokol, H. W., and Valtin, H., 1978, Biosynthetic specificity of neurons producing neurohypophysial principles, in: Current Studies of Hypotha-lamic Function (K. Lederis and W. L Veale, eds.), pp. 62–76, Karger, Basel.Google Scholar
  88. North, W. G., LaRochelle, F. T., Jr., Melton, J., and Mills, R. C., 1980a, Isolation and partial characterization of two human neurophysins: Their use in the development of specific radioimmu-noassays, J. Clin. Endocrinol. Metab. 51: 884–891.PubMedGoogle Scholar
  89. North, W. G., Maurer, L. H., Valtin, H., and O’Donnell, J., 1980b, Human neurophysins as potential tumor markers for small-cell carcinoma of the lung: Application of specific radioimmunoassays for vasopressin-associated and oxytocin-associated neurophysins, J. Clin. Endocrinol. Metab. 51: 892–896.PubMedGoogle Scholar
  90. North, W. G., Mitchell, T. I., and North, G. M., 1982, Characteristics of a precursor to vasopressin-associated bovine neurophysin, FEBS Lett. 152: 29–34.Google Scholar
  91. North, W. G., LaRochelle, F. T., Jr., and Hardy, G. R., 1983a, Development of radioimmunoassays to individual rat neurophysins, J. Endocrinol. 96: 373–386.PubMedGoogle Scholar
  92. North, W. G., Maurer, L. H., and O’Donnell, J. F., 1983b, The neurophysins and small cell cancer, in: Biology and Management of Lung Cancer (F. A. Greco, ed.), pp. 143–170, Martinus Nijhoff, Boston.Google Scholar
  93. North, W. G., Valtin, H., Cheng, S., and Hardy, G. R., 1983c, The neurophysins: Production and turnover, Prog. Brain Res. 60: 217–225.PubMedGoogle Scholar
  94. North, W. G., O’Connor, E., and Gonzalez, C. B., 1985, Structural identification of two provasopres-sins, in: Proceedings of the Sixty-Seventh Meeting of the Endocrinology Society, Baltimore. (Abst. 860.)Google Scholar
  95. Nussey, S. S., Ang, V. T. Y., Jenkins, J. S., Chowdrey, H. S., and Bisset, G. W., 1984, Brattleboro rat adrenal contains vasopressin, Nature (Lond.) 310: 64–66.Google Scholar
  96. Oliver, G., and Schafer, E. A., 1895, On the physiological actions of extracts of the pituitary body and certain other glandular organs, J. Physiol. (Lond.) 18: 277–279.Google Scholar
  97. Pettengill, O. S., Faulkner, C. S., Wurster-Hill, D. H., Maurer, L. H., Sorenson, G. D., Robinson, A. G., and Zimmerman, E. A., 1977, Isolation and characterization of a hormone-producing cell line from human small cell anaplastic carcinoma of the lung, J. Nat I. Cancer Inst. 58: 511–518.Google Scholar
  98. Phelps, C. F., 1980, Glycosylation, in: The Enzymology of Post-translational Modification of Proteins, Vol. 1 (R. B. Freedman and H. C. Hawkins, eds.), pp. 105–155, Academic, London.Google Scholar
  99. Pickering, B. T., 1978, The neurohypophysial neuron: A model for the study of secretion, Essays Bio-chem. 14: 45–81.Google Scholar
  100. Pickering, B. T., Swann, R. W., and Gonzalez, C. B., 1983, Biosynthesis and processing of neurohypophysial hormones, Pharm. Ther. 22: 143–161.Google Scholar
  101. Rabbani, L. D., Pagnozzi, M., Chang, P., and Breslow, E., 1982, Partial digestion of neurophysins with proteolytic enzymes: Unusual interactions between bovine neurophysin II and chymotrypsin, Biochemistry 21: 817–826.PubMedGoogle Scholar
  102. Rhodes, C. H., Morrell, J. L, and Pfaff, D. W., 1981, Changes in the oxytocin content in the magno-cellular neurons of the rat hypothalamus following water deprivation or estrogen treatment. Quantitative immunohistological studies, Cell Tissue Res. 216: 47–55.PubMedGoogle Scholar
  103. Richter, D., Schmale, H., Ivell, R., and Schmidt, C., 1980, Hypothalamic mRNA-directed synthesis of neuropolypeptides: Immunological identification of precursors to neurophysin II, arginine vasopressin and neurophysin I/oxytocin, in: Biosynthesis, Modification and Processing of Cellular and Viral Polyproteins (G. Koch and D. Richter, eds.), pp. 43–66, Academic, New York.Google Scholar
  104. Richter, D., Schmale, H., Ivell, R., and Rehbein, M., 1984, The molecular basis of neurohypophysial hormone expression, in: Endocrinology (F. Labrie and L. Proulx, eds.), pp. 885–890, Elsevier, New York.Google Scholar
  105. Robinson, A. G., Halusczak, C., Wilkins, J. E., Hallmantel, A. B., and Watson, C. G., 1977, Physiologic control of two neurophysins in humans, J. Clin. Endocrinol. Metab. 44: 330–339.PubMedGoogle Scholar
  106. Robinson, I. C. A. F., 1983, Neurohypophysial peptides in cerebrospinal fluid, Prog. Brain Res. 60: 129–146.PubMedGoogle Scholar
  107. Robinson, I. C. A. F., and Jones, P. M., 1983, An intermediate in the biosynthesis of vasopressin and neurophysin in the guinea-pig posterior pituitary, Neurosci. Lett. 39: 273–278.PubMedGoogle Scholar
  108. Rosenior, J. C., North, W. G., and Moore, G. J., 1981, Putative precursors of vasopressin, oxytocin, and neurophysins in the rat hypothalamus, Endocrinology 109: 1067–1072.PubMedGoogle Scholar
  109. Ruppert, S., Scherer, G., and Schutz, G., 1984, Recent gene conversion involving bovine vasopressin and oxytocin precursor genes suggested by nucleotide sequences, Nature (Lond.) 308: 554–557.Google Scholar
  110. Russell, J. T., and Holz, R. W., 1981, Measurement of delta pH and membrane potential in isolated neurosecretory vesicles from bovine neurohypophyses, J. Biol. Chem. 256: 5950–5953.PubMedGoogle Scholar
  111. Russell, J. T., Brownstein, M. J., and Gainer, H., 1979, Trypsin liberates an arginine vasopressin-like peptide and neurophysin from a Mr 20,000 putative common precursor, Proc. Natl. Acad. Sci. U.S.A. 76: 6086–6090.PubMedGoogle Scholar
  112. Russell, J. T., Brownstein, M. J., and Gainer, H., 1980, Biosynthesis of vasopressin, oxytocin and neurophysins: Isolation and characterization of two common precursors (Propressophysin and prooxyphysin), Endocrinology 107: 1880–1891.PubMedGoogle Scholar
  113. Russell, J. T., Brownstein, M. J., and Gainer, H., 1981, Time course of appearance and release of 35cysteine labelled neurophysins and peptides in the neurohypophysis, Brain Res. 205: 299–311.PubMedGoogle Scholar
  114. Sachs, H., and Takabatake, Y., 1964, Evidence for a precursor in vasopressin biosynthesis, Endocrinology 75: 943–948.PubMedGoogle Scholar
  115. Sachs, H., Fawcett, P., Takabatake, Y., and Portanova, R., 1969, Biosynthesis and release of vasopressin and neurophysin, Rec. Prog. Hormone Res. 25: 447–491.Google Scholar
  116. Saermark, T., Thorn, N. A., and Gratzl, M., 1983, Calcium/sodium exchange in purified secretory vesicles from bovine neurohypophysis, Cell Calcium 4: 151–170.PubMedGoogle Scholar
  117. Sawyer, W. H., 1977, Evolution of active neurohypophysial principles among the vertebrates, Am. Zool. 17: 727–737.Google Scholar
  118. Scherman, D., and Nordmann, J. J., 1982, Internal pH of isolated newly formed and aged neurohypophysial vesicles, Proc. Natl. Acad. Sci. U.S.A. 79: 476–479.PubMedGoogle Scholar
  119. Schlesinger, D. H., and Audhya, T. K., 1981, A comparative study of mammalian neurophysin protein sequences, FEBS Lett. 128: 325–328.PubMedGoogle Scholar
  120. Schmale, H., and Richter, D., 1981, Immunological identification of a common precursor to arginine vasopressin and neurophysin II synthesized by in vitro translation of bovine hypothalamic mRNA, Proc. Natl. Acad. Sci. U.S.A. 78: 766–769.PubMedGoogle Scholar
  121. Schmale, H., and Richter, D., 1981, Tryptic release of authentic arginine vasopressin 1–8 from a composite vasopressin, neurophysin II precursor, Neuropeptides 2: 47–52.Google Scholar
  122. Schmale, H., and Richter, D., 1984, Single base deletion in the vasopressin gene is the cause of diabetes insipidus in Brattleboro rats, Nature (Lond.) 308: 705–709.Google Scholar
  123. Schmale, H., Leipold, B., and Richter, D., 1979, Cell-free translation of bovine hypothalamic mRNA, FEBS Lett. 108: 311–316.PubMedGoogle Scholar
  124. Schmale, H., Heinsohn, S., and Richter, D., 1983, Structural organization of the rat gene for the arginine vasopressin-neurophysin precursor, EMBO J. 2: 763–767.PubMedGoogle Scholar
  125. Schmale, H., Ivell, R., Higgins, G., and Richter, D., 1986, Expression of the vasopressin precursor gene in normal and diabetes insipidus rats, in press.Google Scholar
  126. Seidah, N. G., Benjannet, S., and Chretien, M., 1981, The complete sequence of a novel human pituitary glycopeptide homologous to pig posterior pituitary glycopeptide, Biochem. Biophys. Res. Commun. 100: 901–907.PubMedGoogle Scholar
  127. Share, L., 1983, Centrally acting humoral factors in the control of vasopressin release, Prog. Brain Res. 60: 425–435.PubMedGoogle Scholar
  128. Slaninova, J., and Thorn, N. A., 1983, Production of a high affinity antibody specific to the calcium-free-form of calmodulin, using N-acetyl-myramyl-L-alanyle-D-isoglutamine-calmodulin conjugate, J. Immunoassay 4: 395–406.PubMedGoogle Scholar
  129. Smyth, D. G., and Massey, D., 1979, A new glycopeptide in pig, ox and sheep pituitary, Bochem. Biophys. Res. Commun. 87: 1006–1010.Google Scholar
  130. Sofroniew, M. V., 1983, Morphology of vasopressin and oxytocin neurones and their central and vascular projections, Prog. Brain Res. 60: 101–114.PubMedGoogle Scholar
  131. Sokol, H. W., and Valtin, H. (eds.), 1982, The brattleboro rat, Ann. NY. Acad. Sci. 394: 1–828.Google Scholar
  132. Staneloni, R. J., and Leloir, L. F., 1982, The biosynthetic pathway of the asparagine-linked olgosac-charide of glycoproteins, Crit. Rev. Biochem. 12: 298–326.Google Scholar
  133. Steiner, D. F., San Segundo, B., Chan, S. J., and Docherty, K., 1984, Proteolytic mechanisms in pro-hormone processing-cathepsin B-like enzymes in islet secretion vesicles, in: Endocrinology (F. Labrie and L. Proulx, eds.), pp. 387–392, Excerpta Medica, Amsterdam.Google Scholar
  134. Stern, J. E., Mitchell, T., Herzberg, V. L., and North, W. G., 1986, Secretion of vasopressin, oxytocin and two neurophysins from rat hypothalamo-neurohypophyseal expiants in organ culture, Neu-roendocrinology 43: 252–258.Google Scholar
  135. Sunde, D. A., and Sokol, H. W., 1975, Quantification of rat neurophysins by polyacrylamide gel elec-trophoresis: Application to the rat with hereditary hypothalamic diabetes insipidus, Ann. N. Y. Acad. Sci. 248: 345–364.PubMedGoogle Scholar
  136. Swann, W., Gonzalez, C. B., Birkett, S. D., and Pickering, B. T., 1982, Precursors in the biosynthesis of vasopressin and oxytocin in the rat, Biochem. J. 208: 339–349.PubMedGoogle Scholar
  137. Tarentino, A. L., and Maley, F., 1974, Purification and properties of an endo-N-acetylglucaminidase from Streptomyces griseus, J. Biol. Chem. 249: 811–817.PubMedGoogle Scholar
  138. Turner, R. A., Pierce, J. G., and du Vigneaud, V., 1951, The purification and amino acid content of vasopressin preparations, J. Biol. Chem. 191: 21–28.PubMedGoogle Scholar
  139. Valtin, H., Sawyer, W. H., and Sokol, H. W., 1965, Neurohypophysial principles in rats homozygous and heterozygous for hypothalamic diabetes insipidus (Brattleboro strain), Endocrinology 77: 701–706.PubMedGoogle Scholar
  140. Valtin, H., Stewart, J., and Sokol, H. W., 1974, Genetic control of the production of posterior pituitary principles, in: Handbook of Physiology, Section 7, Vol. IV, Part 1: The Pituitary Gland and Its Neuroendocrine Control (E. Knobil and W. H Sawyer, eds.), pp. 131–171, American Physiology Society, Washington, D.C.Google Scholar
  141. Valtin, H., North, W. G., Edwards, B. R., and Gellai, M., 1984, Animal models of diabetes insipidus, Front. Hormone Res. 13: 105–126.Google Scholar
  142. van Leeuwen, F. W., and de Vries, G. J., 1983, Enkephalin glial interaction and its consequence for vasopressin release from the rat neural lobe, Prog. Brain Res. 60: 343–352.PubMedGoogle Scholar
  143. Velden, R. von den, 1913, Die Nierenwirkung von Hypophysenextrakten beim Menschen, Berl. Klin. Wochschr. 50: 2083–2086.Google Scholar
  144. Wang, B. C., Share, L., Crofton, J. T., and Kimura, T., 1982, Effect of intravenous and intracerebro-ventricular infusion of hypertonic solutions on plasma and cerebrospinal fluid vasopressin concentrations, Neuroendocrinology 34: 215–221.PubMedGoogle Scholar
  145. Wang, X.-C, Burbach, J. P. H., Verhoef, J. C., and De Wied, D., 1983, Proteolytic conversion of arginine-vasotocin by supraoptic membranes from rat and chicken brain, Brain Res. 275: 83–90.PubMedGoogle Scholar
  146. Yamaji, T., Ishibashi, M., and Katayama, S., 1981, Nature of the immunoreactive neurophysins in ectopic vasopressin-producing oat cell carcinomas of the lung, J. Clin. Invest. 68: 388–398.PubMedGoogle Scholar
  147. Yamaji, T., Ishibashi, M., and Hori, T., 1984, Propressophysin in human blood: A possible marker of ectopic vasopressin production, J. Clin. Endocrinol. Metab. 59: 505–512.PubMedGoogle Scholar
  148. Yoo, O. J., Powell, C. T., and Pigarwal, K. L., 1982, Molecular cloning and nucleotide sequence of full-length cDNA coding for porcine gastrin, Proc. Natl. Acad. Sci. U.S.A. 79: 1049–1053.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • William G. North
    • 1
  1. 1.Department of PhysiologyDartmouth Medical SchoolHanoverUSA

Personalised recommendations