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Stimulation of amylase release by Orexin is mediated by Orexin 2 receptor in AR42J cells

D M Harris1, V L W Go, J R Reeve

  • 1Center for Human Nutrition, Department of Medicine, UCLA School of Medicine, Los Angeles, CA, USA

Pancreas
|November 1, 2002
PubMed
Abstract

Insights

Orexins stimulate amylase release in pancreatic tumor cells via Orexin receptor 2 (OX2R). This suggests orexins may play a role in pancreatic tumor cell secretion.

Area of Science:

  • Neuroendocrinology
  • Molecular biology
  • Cancer research

Background:

  • Orexins are primarily known for central functions like regulating appetite and sleep.
  • Their peripheral effects, particularly in non-neuronal tissues like the pancreas, are largely uncharacterized.
  • Understanding orexin signaling in pancreatic cells could reveal novel therapeutic targets.

Purpose of the Study:

  • To investigate the expression of orexin receptors (OXR) in the AR42J pancreatic tumor cell line.
  • To determine if orexins, in various forms, can modulate pancreatic cell functions, specifically amylase release and proliferation.

Main Methods:

  • Reverse transcription-PCR (RT-PCR) was used to identify orexin receptor subtypes in AR42J cells.
  • Intracellular calcium mobilization, cAMP levels, and alpha-amylase release were measured upon stimulation with different orexin peptides.
  • Cell proliferation was assessed using H-thymidine incorporation.

Main Results:

  • AR42J cells predominantly express Orexin receptor subtype 2 (OX2R).
  • Orexins A and B induced dose-dependent increases in intracellular calcium and amylase release, but not cAMP accumulation or DNA synthesis.
  • Specific orexin fragments showed reduced activity compared to the full peptides.

Conclusions:

  • Orexin receptor 2 (OX2R) mediates calcium-dependent amylase release in AR42J pancreatic tumor cells.
  • These findings suggest a potential role for orexins in regulating secretory functions within pancreatic tumor cells.

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