Effect of Glutamate Receptor Agonists on Catecholamine Secretion in Bovine Chromaffin Cells

Abstract

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 µM concentration of glutamate agonists was about 20–60% of that obtained with 10 µM 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 µM 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.

Exciting Times beyond the Brain: Metabotropic Glutamate Receptors in Peripheral and Non-Neural Tissues

“…However, L-glutamate stimulates the secretion of catecholamines both in the dog adrenal gland and in chromaffin cells isolated from bovine adrenal medulla (Nishikawa et al, 1982;Gonzá lez et al, 1998). These effects are not caused solely by iGlu receptors; they can be mimicked by the group I mGlu agonists ACPD and DHPG (Gonzá lez et al, 1998;Arce et al, 2004). Arce et al (2004) also report that most of the bovine chromaffin cells isolated from adrenal medulla express group I mGlu receptors, which are at least of two subtypes: mGlu1 and mGlu5a, as demonstrated by immunocytochemistry.…”

“…As for the adrenal gland, no evidence has yet shown a direct action of L-glutamate on glucocorticoid secretion at the adrenal cortex level. However, L-glutamate stimulates the secretion of catecholamines both in the dog adrenal gland and in chromaffin cells isolated from bovine adrenal medulla (Nishikawa et al, 1982;Gonzá lez et al, 1998). These effects are not caused solely by iGlu receptors; they can be mimicked by the group I mGlu agonists ACPD and DHPG (Gonzá lez et al, 1998;Arce et al, 2004).…”

The nerve-heart connection in the pro-oxidant response to Mg-deficiency

“…Although our work suggests SP as the main trigger for the neurogenic inflammation observed during severe Mg deficiency, activation of NMDA receptors may also result in catecholamine release from chromafin cells in the adrenal gland [80,81]. What role circulating catecholamines might have in MgD pathophysiology is still undetermined, although elevated catecholamine release could contribute to the enhanced response to stress seen in MgD [82].…”

Cytosolic organelles shape calcium signals and exo–endocytotic responses of chromaffin cells

“…Ca 2+ entering through nAChRs may contribute to augment vesicle movement and the size of the ready-release vesicle pool [37,38]. Furthermore, glutamate receptors seem to mediate an increase of [Ca 2+ ] c and exocytosis in bovine chromaffin cells [39]. On the other hand, various purinoceptor subtypes that respond to ATP with a [Ca 2+ ] c increase have also been found in these cells [40].…”