Cellular and Molecular Neurobiology

, Volume 8, Issue 1, pp 129–138 | Cite as

Dual regulation of ACTH secretion by guanine nucleotides in permeabilized AtT-20 cells

  • Alberto Luini
  • Maria Antonietta De Matteis
Article

Summary

  1. 1.

    We have examined the effects of guanine nucleotides on ACTH secretion from digitonin-permeabilized AtT-20 cells, with the aim of analyzing the involvement of GTP-binding proteins (G proteins) in the secretory process.

     
  2. 2.

    AtT-20 cells permeabilized with 20µM digitonin displayed calciumdependent secretion. The EC50 of calcium was ~2µM and the maximal stimulation was 350% of basal release.

     
  3. 3.

    Nonhydrolyzable guanine nucleotides also stimulated ACTH release, in a virtually Ca2+-free medium. The EC50 of guanosine 5′-(3-O-thio)triphosphate (GTP γ S) was ~15µM and the maximal stimulation was ~230% of basal release. The effects of calcium and guanine nucleotides were not additive.

     
  4. 4.

    In the presence of the inhibitory hormone, somatostatin guanine nucleotides inhibited the calcium-stimulated secretion.

     
  5. 5.

    Both the stimulatory and the inhibitory effects on secretion of guanine nucleotides were independent of changes in cyclic AMP (cAMP) and calcium. It is suggested that G proteins influence an unknown step in the secretion process, which would be near or at the exocytotic site.

     
  6. 6.

    The results can be explained by assuming the existence of two types of G proteins, one with stimulatory effects on exocytotic release (GeS) and another with inhibitory effects (GeI).

     

Key words

GTP-binding proteins calcium exocytosis guanine nucleotides adrenocorticotropic hormone (ACTH) AtT-20 cells 

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Copyright information

© Plenum Publishing Corporation 1988

Authors and Affiliations

  • Alberto Luini
    • 1
  • Maria Antonietta De Matteis
    • 1
  1. 1.Neuroendocrinology UnitIstituto di Ricerche Farmacologiche Mario NegriS. Maria ImbaroItaly

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