Hormone secretagogues increase cytosolic calcium by increasing cAMP in corticotropin-secreting cells

A. Luini, D. Lewis, S. Guild, D. Corda, J. Axelrod

Research output: Contribution to journalArticle

Abstract

Corticotropin (ACTH)-releasing factor, vasoactive intestinal peptide, and catecholamines - hormones that stimulate ACTH secretion and cAMP generation - increased cytosolic calcium in AtT-20 cells. The increase in intracellular calcium is presumably a consequence of the stimulated cAMP synthesis, since forskolin, an activator of the catalytic unit of adenylate cyclase, and the cAMP analog 8-bromoadenosine 3',5'-cyclic monophosphate (8Br-cAMP) also increased the cytosolic levels of this ion. Pretreatment with somatostatin, a neuropeptide that inhibits stimulation of the adenylate cyclase system and the secretion of ACTH blocked the increase of cytosolic calcium. The effect of 8Br-cAMP, which bypasses the cyclase, was not inhibited by somatostatin pretreatment. The source of the increased calcium appears to be mainly extracellular. This is indicated by the inability of the secretagogues to increase cytosolic calcium in a medium deprived of this ion or in the presence of blockers of voltage-gated calcium channels. The involvement of calcium channels in the calcium rise evoked by the secretagogues was supported by experiments using the whole-cell patch-clamp technique. In these experiments 8Br-cAMP increased voltage-dependent calcium currents. These results suggest the following chain of events in the receptor-mediated elevation of cytosolic calcium and the concomitant release of ACTH from AtT-20 cells: hormone-receptor binding ≥ cAMP synthesis ≥ protein kinase activation ≥ calcium channel activation ≥ increase in cytosolic calcium ≥ many steps ≥ ACTH release. Phorbol myristate acetate, a compound which does not stimulate cAMP generation but enhances the release of ACTH in AtT-20 cells, decreased the cytosolic calcium level.

Original languageEnglish
Pages (from-to)8034-8038
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume82
Issue number23
DOIs
Publication statusPublished - 1985

ASJC Scopus subject areas

  • Genetics
  • General

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