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Evidence for high peptide alpha-amidating activity in the pancrease from neonatal rats.

L Ouafik, P Giraud, P Salers

    Proceedings of the National Academy of Sciences of the United States of America
    |January 1, 1987
    PubMed
    Summary
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    Neonatal rat pancreas exhibits high peptidylglycine alpha-amidating mono-oxygenase (PAMase) activity, crucial for thyrotropin-releasing hormone (TRH) biosynthesis. This enzyme and TRH levels are similarly regulated during development, offering a unique endocrine model.

    Area of Science:

    • Endocrinology
    • Neuroscience
    • Biochemistry

    Background:

    • High peptidylglycine alpha-amidating mono-oxygenase (PAMase) activity is found in neonatal rat pancreas.
    • A significant portion of this activity is localized in pancreatic beta cells, co-occurring with thyrotropin-releasing hormone (TRH) and its precursor in secretory granules.

    Purpose of the Study:

    • To investigate the role and regulation of PAMase activity in the neonatal rat pancreas.
    • To explore the relationship between PAMase activity and TRH biosynthesis in this model.
    • To examine the ontogenetic changes of PAMase and its potential involvement in other amidated peptides.

    Main Methods:

    • Measurement of PAMase activity in neonatal rat pancreas.
    • Localization studies within pancreatic beta cells and secretory granules.

    Related Experiment Videos

  • Incubation experiments to assess PAMase's ability to generate TRH from precursor fragments.
  • Analysis of ontogenetic variations in PAMase activity and TRH concentrations.
  • Main Results:

    • PAMase activity in the neonatal rat pancreas parallels TRH concentrations during development.
    • PAMase can generate TRH from the tetrapeptide Glu-His-Pro-Gly, a sequence found in the TRH precursor.
    • Ontogenetic changes suggest similar regulation of TRH precursor and PAMase activity.
    • Evidence suggests PAMase activity may also contribute to the biosynthesis of other amidated peptides beyond TRH.

    Conclusions:

    • The neonatal rat pancreas serves as a valuable endocrine model for studying the co-regulation of neuropeptide precursors and post-translational modifying enzymes.
    • PAMase plays a significant role in TRH biosynthesis in the neonatal pancreas.
    • PAMase activity is involved in the synthesis of other amidated peptides, with synthesis peaking during the neonatal period.