Pharmacological and molecular characterization of glutamate receptors in the MIN6 pancreatic β-cell line

Paul Morley, Sue MacLean, Tania F. Gendron, Daniel L. Small, Roger Tremblay, Jon P. Durkin, Geoffrey Mealing

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The MIN6 pancreatic β-cell line responds to glutamate, α-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate, but not N- methyl-D-aspartate (NMDA) or 1S,3R-trans-ACPD, with increases in [Ca2+](i). This correlates with MIN6 expression of AMPA receptor subunits (GluR1-4) but only weak expression of NMDA NR2 receptor subunits, as determined by reverse transcriptase polymerase chain reaction (RT-PCR). Pharmacological characterization of the MIN6 AMPA receptors showed that AMPA-triggered [Ca2+](i) responses were blocked by GYKI 52466, 6-cyano-7-nitroquinoxaline- 2,3-dione (CNQX) and pentobarbital. AMPA-triggered [Ca2+ ](i) responses were also blocked in Na+-free medium and by the voltage-sensitive Ca2+ channel antagonist La3+. Unlike cortical neuronal cultures, which show a loss of membrane-associated protein kinase C (PKC) activity and die in response to excitatory amino acid exposure, glutamate was not toxic to MIM6 cells and it did not decrease PKC activity. These studies indicate that MIN6 cells possess Ca2+-impermeable AMPA receptors that secondarily allow Ca2+ influx following AMPA-induced depolarization and that, despite elevating [Ca2+](i), AMPA is not toxic to these cells. The effects of glutamate and glutamate receptor antagonists on pancreatic cells needs to be better understood if these compounds are to be used as therapeutic agents to treat stroke.

Original languageEnglish (US)
Pages (from-to)379-385
Number of pages7
JournalNeurological research
Volume22
Issue number4
DOIs
StatePublished - Jan 1 2000

Keywords

  • AMPA
  • Ca
  • MIN6
  • NMDA
  • Pancreas
  • Protein kinase C

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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