Expression of functional GABAA receptors in isolated human insulinoma cells

Ann N Y Acad Sci. 1998 Nov 17:859:241-8. doi: 10.1111/j.1749-6632.1998.tb11138.x.

Abstract

Pancreatic islets contain and release high concentrations of GABA. GABA is thought to play a paracrine role in beta-cells. Searching for a paracrine function of GABA in neoplastic beta-cells we performed patch-clamp studies in isolated human insulinoma cells. We show that human insulinoma cells can express functional GABAA receptors. Activation of GABAA receptors caused a reversible membrane depolarization in a subgroup of insulinoma cells. Membrane depolarization resulted in transmembraneous calcium influx through voltage-gated calcium channels and stimulation of insulin secretion. Insulin secretion was increased by the GABAA receptor agonist muscimol (50 microM) by about 280%. Thus, GABAA receptors can be expressed in human insulinoma cells and can regulate their insulin release.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadmium Chloride / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / physiology
  • Female
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Insulinoma / pathology
  • Insulinoma / physiopathology*
  • Insulinoma / surgery
  • Isradipine / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Middle Aged
  • Muscimol / pharmacology
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / physiopathology*
  • Pancreatic Neoplasms / surgery
  • Patch-Clamp Techniques
  • Picrotoxin / pharmacology
  • Receptors, GABA-A / physiology*
  • Tumor Cells, Cultured
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Insulin
  • Receptors, GABA-A
  • Picrotoxin
  • Muscimol
  • gamma-Aminobutyric Acid
  • Cadmium Chloride
  • Isradipine