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How does histamine evoke catecholamine secretion from bovine chromaffin cells?

Philip D Marley1, Damian Wallace, Amanda Donald

  • 1Department of Pharmacology, University of Melbourne, Victoria 3010, Australia. p.marley@unimelb.edu.au

Annals of the New York Academy of Sciences
|November 20, 2002
PubMed

Insights

Histamine triggers catecholamine secretion from bovine chromaffin cells by inhibiting an M current, leading to cell depolarization and action potential firing. This process is independent of common signaling pathways and ion concentrations.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Endocrinology

Background:

  • Bovine chromaffin cells are a model system for studying stimulus-secretion coupling.
  • Catecholamine secretion is crucial for the body's stress response.
  • The precise mechanisms of histamine-evoked catecholamine release are not fully understood.

Purpose of the Study:

  • To investigate the signaling pathways involved in histamine-evoked catecholamine secretion from bovine chromaffin cells.
  • To elucidate the role of M-current inhibition in histamine-induced cellular responses.

Main Methods:

  • Bovine chromaffin cells were utilized for secretion assays.
  • Inhibitors of inositol trisphosphate (IP3) receptors, protein kinase C (PKC), and phospholipase C (PLC) were employed.
  • Calcium (Ca2+) stores were depleted, and extracellular sodium (Na+) and chloride (Cl-) were omitted.
  • Patch clamp electrophysiology was used to study ion channel activity.

Main Results:

  • Histamine-evoked catecholamine secretion was not inhibited by IP3 receptor blockers, PKC inhibitors, or PLC inhibitors.
  • Secretion proceeded even when Ca2+ stores were depleted or extracellular Na+ or Cl- were absent.
  • Patch clamp recordings revealed that histamine inhibited an M current in these cells.
  • This M current inhibition resulted in cell depolarization and the firing of action potentials.

Conclusions:

  • Histamine-evoked catecholamine secretion from bovine chromaffin cells occurs through a novel pathway.
  • Inhibition of the M current by histamine is the primary mechanism driving depolarization and subsequent secretion.
  • This mechanism is independent of classical IP3, PKC, PLC, and Ca2+ store depletion pathways.

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