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

Alberto Luini, Maria Antonietta De Matteis

Research output: Contribution to journalArticle

Abstract

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. AtT-20 cells permeabilized with 20 μM digitonin displayed calciumdependent secretion. The EC50 of calcium was ~2 μM and the maximal stimulation was 350% of basal release. 3. Nonhydrolyzable guanine nucleotides also stimulated ACTH release, in a virtually Ca2+-free medium. The EC50 of guanosine 5′-(3-O-thio)triphosphate (GTPγS) was ~15 μM and the maximal stimulation was ~230% of basal release. The effects of calcium and guanine nucleotides were not additive. 4. In the presence of the inhibitory hormone, somatostatin guanine nucleotides inhibited the calcium-stimulated secretion. 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. 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).

Original languageEnglish
Pages (from-to)129-138
Number of pages10
JournalCellular and Molecular Neurobiology
Volume8
Issue number1
DOIs
Publication statusPublished - Mar 1988

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Genetics
  • Clinical Biochemistry
  • Cell Biology
  • Cellular and Molecular Neuroscience

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