Biosynthesis of the Tachykinins and Somatostatin

  • Anthony J. Harmar
  • Adrian R. Pierotti
  • Peter Keen
Part of the Biochemical Endocrinology book series (BIOEND)


There are two mechanisms by which the expression of a single neuropeptide gene may, in different tissues, give rise to alternative patterns of biologically active peptides:
  1. 1)

    Tissue-specific RNA splicing of a single gene transcript may result in the generation of messenger RNA (mRNA) species encoding different polypeptide precursors, which may be processed into different products. For example, transcription of the calcitonin gene in thyroid tissue results in the production of a mRNA encoding the calcitonin precursor, whereas in nervous tissue a mRNA encoding the neuropeptide calcitonin gene-related peptide (C6RP) is generated (Rosenfeld et al., 1983; Craig et al., this volume).

  2. 2)

    Tissue-specific post-translational modifications of a single polypeptide precursor may generate different polypeptide products. The best known example is pro-opiomelanocortin, the common precursor to adrenocorticotrophic hormone (ACTH), the melanocyte-stimulating hormone (α, β- and γ-MSH) and the endorphin family of opioid peptides. In the anterior pituitary gland, the predominant products of POMC processing are ACTH and β-endorphin, whereas in the pars intermedia αMSH, corticotrophin-like intermediate lobe peptide (CLIP) and acetylated, biologically inactive forms of endorphin are produced (Krieger & Liotta, 1979).



High Performance Liquid Chromatography Dorsal Root Ganglion Median Eminence Tachykinin Receptor Polypeptide Precursor 
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. Baskin, D.G. and Ensinck, J.W., 1984, Somatostatin in epithelial cells of intestinal mucosa is present primarily as somatostatin 28, Peptides, 5:615.PubMedCrossRefGoogle Scholar
  2. Benoit, R., Bohlen, P., Esch, F. and Ling, M., 1984, Neuropeptides derived from prosomatostatin that do not contain the somatostatin-14 sequence, Brain Res. 311:23.PubMedCrossRefGoogle Scholar
  3. Benoit, R., Bohlen, P., Ling, N., Briskin, A., Esch, F. Brazeau, P., Ying, S-Y and Guillemin, R., 1982, Presence of somatostatin 28 (1–12) in hypothalamus and pancreas, Proc. Natn. Acad. Sci. U.S.A. 79:917.CrossRefGoogle Scholar
  4. Benoit, R., Ling, N., Alford, B. and Guillemin, R., 1982, Seven peptides derived from pro-somatostatin in rat brain, Biochem. Biophys. Res. Commun. 107:944.PubMedCrossRefGoogle Scholar
  5. Brazeau, P., Ling, N., Esch, F., Bohlen, P., Benoit, R. and Guillemin, R., 1981, High biological activity of the synthetic replicates of somatostatin-28 and somatostatin-25, Reg. Peptides 1:255.CrossRefGoogle Scholar
  6. Daikoku, S., Hisano, S., Kawano, H., Okamura, Y. and Tsuruo, Y., 1983, Ontogenetic studies on the topographical heterogeneity of somatostatin-containing neurones in rat hypothalamus, Cell Tissue Res. 233:347.PubMedCrossRefGoogle Scholar
  7. Erspamer, V., 1981, The tachykinin peptide family, Trends Neurosci. 4:267.CrossRefGoogle Scholar
  8. Goodman, R.H., Aron, D.C. and Roos, B.A., 1983, Rat prepro-somatostatin, structure and processing by microsomal membranes, J. Biol. Chem. 258:5570.PubMedGoogle Scholar
  9. Harmar, A.J. and Keen, P., 1982, Synthesis, and central and peripheral axonal transport of substance P in a dorsal root ganglion-nerve preparation in vitro, Brain Res. 231:379.PubMedCrossRefGoogle Scholar
  10. Harmar, A.J. and Keen, P., 1984, Rat sensory ganglia incorporate radiolabelled amino acids into substance K (neurokinin α) in vitro, Neurosci. Letts. 51:387.CrossRefGoogle Scholar
  11. Harmar, A.J., Ivell, R. and Keen, P., 1982, The de novo biosynthesis of somatostatin and a related peptide in isolated rat dorsal root ganglia, Brain Res. 242:365.PubMedCrossRefGoogle Scholar
  12. Harmar, A.J., Schofield, J.G. and Keen, P., 1981, Substance P biosynthesis in dorsal root ganglia: An immunochemical study of [35S]-methionine and [3H]-proline incorporation in vitro, Neuroscience 6:19172.CrossRefGoogle Scholar
  13. Hokfelt, T., Eide, R., Johansson, O., Luft, R., Nilsson, G. and Arimura, A., 1976, Immunohistochemical evidence for separate populations of somatostatin-containing and substance P-containing primary afferent neurons in the rat, Neuroscience 1:131.PubMedCrossRefGoogle Scholar
  14. Iversen, L.L., Hanley, M.R., Sandberg, B.E.B., Lee, C.M., Pinnock, R.D. and Watson, S.P., 1982, Substance P receptors in the nervous system and possible receptor subtypes, in: “Substance P in the nervous system,” R. Porter and M. O’Connor, eds., Pitman, London.Google Scholar
  15. Kawano, H., Diakoku, S. and Saito, S., 1982, Immunohistochemical studies of intrahypothalamic somatostatin-containing neurones in rat, Brain Res. 242:227.PubMedCrossRefGoogle Scholar
  16. Kewley, C.F., Millar, R.P., Berman, M.C. and Schally, A.V., 1981, Depolarization-and ionophore-induced release of octacosa somatostatin from stalk median eminence synaptosomes, Science 213:913.PubMedCrossRefGoogle Scholar
  17. Kimura, S., Oada, M., Sugita, Y., Kanazawa, I. and Munekata, E., 1983, Novel neuropeptides, neurokinin α and β, isolated from porcine spinal cord, Proc. Japan. Acad, Ser. B., 59:101.CrossRefGoogle Scholar
  18. Krieger, D.T. and Liotta, A.F. 1979, Pituitary hormones in brain: where, how and why?, Science, 205:366.PubMedCrossRefGoogle Scholar
  19. Larsson, L.I. and Rehfeld, J.F., 1979, Localization and molecular heterogeneity of cholecystokinin in the central and peripheral nervous system, Brain Res. 165: 201.PubMedCrossRefGoogle Scholar
  20. Lee, C-M., Emson, P.C. and Iversen, L.L., 1980, The development and application of a novel N-terminal directed substance P antiserum, Life Sci. 27:535.PubMedCrossRefGoogle Scholar
  21. Lundberg, J.M., Hokfelt, T., Nilsson, G., Terenius, L. and Rehfeld, J. R. Eide and S. Said, (1978), Acta physioi. Scand. 104, 499.CrossRefGoogle Scholar
  22. Mandarino, L., Stenner, D., Blanchard, W., Nissen, S., Gerich, J., Ling, N., Brazeau, P., Bohlen, P., Esch, F. and Guillemin, R., 1981, Selective effects of somatostatin-14,25,28 on in vitro insulin and glucagon secretion, Nature 291:767.CrossRefGoogle Scholar
  23. Millar, R.P., Sheward, W.J., Wegener, I. and Fink, G., 1983, Somatostatin-28 is a hormonally active peptide released into hypophysial portal vessel blood, Brain Res. 260:334.PubMedCrossRefGoogle Scholar
  24. Nawa, H., Hirose, T., Takashima, H., Inayama S & Nakanishi, S., 1983, Nucleotide sequence of cloned cDNAs for two types of bovine brain substance P precursor, Nature 306:32.PubMedCrossRefGoogle Scholar
  25. Nawa, H., Kotani, H. and Nakaniski, S., 1984, Tissue-specific generation of two preprotachykinin mRNAs from one gene by alternative RNA splicing, Nature 312:729.PubMedCrossRefGoogle Scholar
  26. Pierotti, A.R. and Harmar, A.J., 1985, Multiple forms of somatostatin-like immunoreactivity in the hypothalamus and amygdala of the rat: selective localization of somatostatin-28 in the median eminence, J. Endocrinol. 105:383.PubMedCrossRefGoogle Scholar
  27. Pierotti, A.R., Harmar, A.J., Tannahill, L. and Arbuthnott, G.W., 1985, Different patterns of molecular forms of somatostatin are released by the rat median eminence and hypothalamus, Neurosci. Letts. 57:215.CrossRefGoogle Scholar
  28. Pradayrol, L., Jornvall, H., Mutt, V. and Ribet, A., 1980, N-terminally extended somatostatin: the primary structure of somatostatin-28, FEBS Lett. 109:55.PubMedCrossRefGoogle Scholar
  29. Ravazzola, M., Benoit, R., Ling, N., Guillemin, R. and Orci, L., 1983, Immunocytochemical localization of prosomatostatin fragments in maturing and mature secretory granules of pancreatic and gastrointestinal D-cells, Proc. Natn. Acad. Sci. U.S.A. 80:215.CrossRefGoogle Scholar
  30. Rosenfeld, M.G., Mermod, J-J., Amara, S.G., Swanson, L.W., Sawchenko, P.E. Rivier, J., Vale, W.W. and Evans, R.M., 1983, Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing, Nature 304:129.PubMedCrossRefGoogle Scholar
  31. Srikant, C.B. and Patel, Y.C., 1981, Receptor binding of somatostatin-28 is tissue specific, Nature 294:259.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Anthony J. Harmar
    • 1
  • Adrian R. Pierotti
    • 1
  • Peter Keen
    • 2
  1. 1.MRC Brain Metabolism UnitRoyal Edinburgh HospitalEdinburghUK
  2. 2.University Department of PharmacologyBristolUK

Personalised recommendations