Effect of glutamate receptor agonists on catecholamine secretion in bovine chromaffin cells

Neuroendocrinology. 1998 Mar;67(3):181-9. doi: 10.1159/000054313.


In this study, the effects of glutamate and glutamate receptor agonists in cultured chromaffin cells from bovine adrenal medulla were investigated. It was found that glutamate increases basal catecholamine (CA) secretion in a dose-dependent manner. This effect is mimicked by specific agonists of the four known glutamate receptors N-methyl-D-aspartate (NMDA), quisqualate/(RS)-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate (KA), and trans-(+)-1-amino-1,3-cyclopentane dicarboxylic acid (t-ACPD), which increased both basal and nicotine-evoked CA secretion. The NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid, 6-cyano-7-nitroquinoxaline-2,3-dione, an antagonist of KA and AMPA receptors, and L-(+)-2-amino-3-phosphonopropionic acid, an antagonist of the t-ACPD receptor, inhibited the stimulatory effect of related glutamate agonists. Hexamethonium, an antagonist of the nicotinic receptor, failed to influence glutamate agonists except for a 15% inhibition of KA. The increase in CA secretion produced by a 100 microM concentration of glutamate agonists was about 20-60% of that obtained with 10 microM of nicotine, an agonist of the physiological stimulatory cholinergic receptor. The increase in CA secretion produced by glutamate was accompanied by both an increase in bisoxonol fluorescence, suggesting membrane depolarization, and by an increase in intracellular Ca2+ concentrations. Results obtained with image analysis on single cells indicated that the percentage of cells which respond to the stimulation of 50 microM of glutamate is 42%. From these results, we conclude that glutamate, through its four known glutamate receptors, can increase both basal and nicotine-evoked CA secretion in chromaffin cells by a process which involves membrane depolarization and an increase in intracellular calcium levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Medulla / drug effects
  • Adrenal Medulla / metabolism
  • Animals
  • Catecholamines / metabolism*
  • Cattle
  • Cells, Cultured
  • Chromaffin System / drug effects*
  • Chromaffin System / metabolism*
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology*
  • Glutamic Acid / blood
  • Glutamic Acid / pharmacology
  • Kainic Acid / pharmacology
  • Membrane Potentials / drug effects
  • N-Methylaspartate / pharmacology
  • Nicotine / pharmacology
  • Receptors, Glutamate / drug effects
  • Receptors, Glutamate / physiology*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology


  • Catecholamines
  • Excitatory Amino Acid Agonists
  • Receptors, Glutamate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • Glutamic Acid
  • N-Methylaspartate
  • Nicotine
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Kainic Acid