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  2. Abstract

In 1977 a nonapeptide, called delta-sleep-inducing peptide (DSIP) was characterized in rabbit cerebral venous blood plasma during thalamic stimulation to induce sleep. Evidence for the existence of DSIP in the central nervous system and in numerous peripheral organs of various mammalian species has been obtained using immunochemical techniques. Later findings have revealed the existence of large forms of DSIP-like immunoreactivity. We decided to investigate the molecular identity of such large forms of DSIP-like immunoreactivity by direct isolation. We have purified and characterized using amino acid analysis, sequencing, mass spectrometry and radioimmunoassay a 77-residue peptide, denoted DIP (DSIP-immunoreactive peptide), from an acid extract of porcine brain. DIP is recognized by an antiserum raised against synthetic rabbit DSIP. The amino acid sequence of DIP, however, is not related to that of DSIP, but it contains a putative leucine-zipper motif, a proline/glutamic-acid-rich domain, three potential phosphorylation sites and exhibits an acetylated N-terminus. The N-terminal but not the C-terminal part of the newly isolated peptide shares clear homology with the sequence of a protein induced by transforming growth factor β1 and other growth factors in mouse osteoblastic cells. DIP is also structurally similar to a baculoviral protein p10. The function of DIP remains unclear but its involvement in transcriptional regulation is probable.


cardiodilatin/atrial natriuretic factor


delta-sleep-inducing-peptide-immunoreactive peptide


delta-sleep-inducing peptide


delta-sleep-inducing-peptide-like immunoreactivity


Endoproteinase Glu-C (EC


endoproteinase Lys-C (EC


carboxypeptidase P from Penicillum janthinellum (EC


elastase (EC


thermolysin (EC


trypsin (EC


  1. Top of page
  2. Abstract
  • 1
    Monnier, M., Dudler, L., Gächter, R., Maler, P. F., Tobler, H. J. & Schoenenberger, G. A. (1977) The delta sleep inducing peptide (DSIP). Comparative properties of the original and synthetic nonapeptide, Experientia (Basel) 33, 548552.
  • 2
    Schoenenberger, G. A. & Monnier, M. (1977) Characterization of a delta-electroencephalogram (-sleep)-inducing peptide, Proc. Natl Acad. Sci. USA 74, 12821286.
  • 3
    Schoenenberger, G. A., Maier, P. F., Tobler, H. J. & Monnier, M. (1977) A naturally occurring delta-EEG-enhancing nonapeptide in rabbits. X. Final isolation, characterization and activity test, Eur. J. Physiol. 369, 99109.
  • 4
    Graf, M. V. & Kastin, A. J. (1984) Delta-sleep-inducing peptide (DSIP): an review, Neurosci. Biobehav. Rev. 8, 8393.
  • 5
    Graf, M. V. & Kastin, A. J. (1986) Delta-sleep-inducing peptide (DSIP) van update, Peptides (Elmsford) 7, 11651187.
  • 6
    Bjartell, A., Ekman, R., Hedenbro, J., Sjölund, K. & Sundler, F. (1989) Delta sleep-inducing peptide (DSIP)-like immunoreactivity in gut: coexistence with known peptide hormones. Peptides (Elmsford) 10, 163170.
  • 7
    Feldman, S. C. & Kastin, A. J. (1984) Localization of neurons containing immunoreactive delta sleep-inducing peptide in the rat brain: an immunocytochemical study, Neuroscience 11, 303317.
  • 8
    Feldman, S. C. & Kastin, A. J. (1984) The distribution of neurons containing delta sleep-inducing peptide in the hippocampal formation, Brain Res. Bull. 13, 833837.
  • 9
    Kastin, A. J., Nissen, C., Schally, A. V. & Coy, D. H. (1978) Radioimmunoassay of DSIP-like material in rat brain, Brain Res. Bull. 3, 691695.
  • 10
    Graf, M. V., Kastin, A. J. & Fischman, A. J. (1984) DSIP occurs in free form in mammalian plasma, human CSF and urine, Pharmacol. Biochem. Behav. 21, 761766.
  • 11
    Graf, M. V. & Kastin, A. J. (1984) Delta sleep-inducing peptide (DSIP)-like material exists in peripheral organs of rats in large dissociable forms, Proc. Soc. Exp. Biol. Med. 177, 197204.
  • 12
    Kastin, A. J., Castellanos, P. F., Banks, W. A. & Coy, D. H. (1981) Radioimmunoassay of DSIP-like material in human blood: possible protien binding, Pharmacol. Biochem. Behav. 15, 969974.
  • 13
    Noteborn, H. P., Graf, M. V., Ernst, A., Schoenenberger, G. A., Weusten, J. A., Ebels, I. & Salemink, C. A. (1988) Purification and characterization of DSIP-like material from ovine pineal glands: possible peptide-protein interaction, J. Pineal. Res. 5, 161177.
  • 14
    Shibanuma, M., Kuroki, T. & Nose, K. (1992) Isolation of a gene encoding a putative leucine zipper structure that is induced by transforming growth factor β1 and other growth factors, J. Biol. Chem. 267, 1021910224.
  • 15
    Leisy, D. J., Rohrmann, G. F., Nesson, M. & Beaudreau, G. S. (1986) Nucleotide sequencing and transcriptional mapping of the Orygia pseudotsugata multicapsid nuclear polyhedrosis virus p10 gene, Virology 153, 157167.
  • 16
    Landschulz, W. H., Johnson, P. F. & McKnight, S. L. (1988) The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins, Science 240, 17591764.
  • 17
    McCormack, K., Campanelli, J. T., Ramaswami, M., Mathew, M. K. & Tanouye, M. A. (1989) Leucine zipper motif update, Nature 340, 103.
  • 18
    White, M. K. & Weber, M. J. (1989) Leucine zipper motif update, Nature 340, 103.
  • 19
    Kouzarides, T. & Ziff, E. (1988) The role of the leucine zipper in the fos-jun interaction, Nature 336, 646651.
  • 20
    Buckland, R. & Wild, F. (1989) Leucine zipper motif extends, Nature 338, 547.
  • 21
    O'Shea, E. K., Klemm, J. D., Kim, P. S. & Alber, T. (1991) X-ray structure of the GCN4 leucine zipper, a two-stranded, parallel coiled coil, Science 254, 539544.
  • 22
    Rasmussen, R., Benvegnu, D., O'Shea, E. K., Kim, P. S. & Alber, T. (1991) X-ray scattering indicates that lecine zipper is a coiled coil, Proc. Natl Acad. Sci. USA 88, 561564.
  • 23
    Kennelly, P. J. & Krebs, E. G. (1991) Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases, J. Biol. Chem. 266, 1555515558.
  • 24
    Wegner, M., Cao, Z. & Rosenfeld, M. G. (1992) Calcium-regulated phosphorylation within the leucine zipper of C/EBPβ, Science 256, 370373.
  • 25
    Yamamoto, K. K., Gonzales, G. A., Biggs III, W. H. & Montminy, M. R. (1988) Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB, Nature 334, 494498.
  • 26
    Odell, W. D. & Franchimont, P. (1983) Principles of competitive protein-binding assays, J. Wiley and Sons, New York , Brisbane .
  • 27
    Sillard, R., Rökaeus, Å, Xu, Y., Carlquist, M., Bergman, T., Jörnvall, H. & Mutt, V. (1992) Variant forms of galanin isolated from porcine brain, Peptides (Elmsford) 13, 10551060.
  • 28
    Mutt, V., Carlquist, M. & Tatemoto, K. (1979) Secretin-like bioacitivity in extracts of porcine brain, Life. Sci. 25, 17031708.
  • 29
    Mutt, V. (1988) Vasoactive intestinal peptide and related peptides. Isolation and chemistry, Ann. NY Acad. Sci. 527, 119.
  • 30
    Deverux, J., Haeberli, P. & Smithies, O. (1984) A comprehensive set of sequence analysis programs for VAX and Convex systems, Nucleic Acids Res. 12, 387395.