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Characterization of Ca2(+)-mobilizing excitatory amino acid receptors in cultured chick cortical cells.
Eur J Pharmacol. 1990 Oct 30; 189(4-5):253-66.EJ

Abstract

The effects of glutamate and other more selective excitatory amino acid (EAA) analogs on intracellular free calcium concentration ([Ca2+]i) were examined in Fura 2-loaded cultured chick embryo cortical cells (90% neuronal). Four EAA receptors were evident in these studies: an N-methyl-D-aspartate (NMDA) receptor, a kainate receptor, and two quisqualate receptors. The [Ca2+]i response to NMDA was blocked or reversed by selective antagonists such as 2-amino-5-phosphonovalerate (APV), MK801 and ketamine, as well as by desmethylimipramine and dextromethorphan. Glycine potentiated the [Ca2+]i response to NMDA, and high concentrations of glycine selectively overcame blockade by kynurenic acid, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and cis-piperidine-2,3-dicarboxylic acid (PDA). The [(Ca2+]i response to kainate was generally larger than the NMDA response, and the kainate response desensitized slightly over the first minute. CNQX was more potent as an antagonist of the kainate response than of the NMDA response, even in the absence of added glycine; kynurenic acid and PDA conversely had little effect on the kainate response in these cells at concentrations which blocked the NMDA response. The desensitization of the [Ca2+]i response to kainate was greatly augmented by quisqualate and by the putative ionotropic quisqualate receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). In the absence of kainate, both quisqualate and AMPA increased [Ca2+]i though less so than did NMDA or kainate. Quisqualate (and AMPA and glutamate) were not acting as partial agonists at the kainate receptor, since the potency of these agonists in reversing the kainate [Ca2+]i response was independent of kainate concentration. Quisqualate, but not AMPA, also produced a small increase in [Ca2+]i which preceded the negative effect of this agonist on the kainate response. This increase in [Ca2+]i could also be evoked by quisqualate or glutamate after inhibition of the kainate response by AMPA. Quisqualate and glutamate, but not the other EAA agonists, also increased [Ca2+]i after chelation of extracellular calcium with EGTA. This effect appears to be mediated by the metabotropic quisqualate receptor. These cells should provide a useful system for studying regulation and interactions of EAA receptors, and for screening drugs which might act at these receptors.

Authors+Show Affiliations

Department of Psychiatry, Tufts University School of Medicine, New England Medical Center, Boston, MA 02111.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1980647

Citation

McMillian, M, et al. "Characterization of Ca2(+)-mobilizing Excitatory Amino Acid Receptors in Cultured Chick Cortical Cells." European Journal of Pharmacology, vol. 189, no. 4-5, 1990, pp. 253-66.
McMillian M, Pritchard GA, Miller LG. Characterization of Ca2(+)-mobilizing excitatory amino acid receptors in cultured chick cortical cells. Eur J Pharmacol. 1990;189(4-5):253-66.
McMillian, M., Pritchard, G. A., & Miller, L. G. (1990). Characterization of Ca2(+)-mobilizing excitatory amino acid receptors in cultured chick cortical cells. European Journal of Pharmacology, 189(4-5), 253-66.
McMillian M, Pritchard GA, Miller LG. Characterization of Ca2(+)-mobilizing Excitatory Amino Acid Receptors in Cultured Chick Cortical Cells. Eur J Pharmacol. 1990 Oct 30;189(4-5):253-66. PubMed PMID: 1980647.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of Ca2(+)-mobilizing excitatory amino acid receptors in cultured chick cortical cells. AU - McMillian,M, AU - Pritchard,G A, AU - Miller,L G, PY - 1990/10/30/pubmed PY - 1990/10/30/medline PY - 1990/10/30/entrez SP - 253 EP - 66 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 189 IS - 4-5 N2 - The effects of glutamate and other more selective excitatory amino acid (EAA) analogs on intracellular free calcium concentration ([Ca2+]i) were examined in Fura 2-loaded cultured chick embryo cortical cells (90% neuronal). Four EAA receptors were evident in these studies: an N-methyl-D-aspartate (NMDA) receptor, a kainate receptor, and two quisqualate receptors. The [Ca2+]i response to NMDA was blocked or reversed by selective antagonists such as 2-amino-5-phosphonovalerate (APV), MK801 and ketamine, as well as by desmethylimipramine and dextromethorphan. Glycine potentiated the [Ca2+]i response to NMDA, and high concentrations of glycine selectively overcame blockade by kynurenic acid, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and cis-piperidine-2,3-dicarboxylic acid (PDA). The [(Ca2+]i response to kainate was generally larger than the NMDA response, and the kainate response desensitized slightly over the first minute. CNQX was more potent as an antagonist of the kainate response than of the NMDA response, even in the absence of added glycine; kynurenic acid and PDA conversely had little effect on the kainate response in these cells at concentrations which blocked the NMDA response. The desensitization of the [Ca2+]i response to kainate was greatly augmented by quisqualate and by the putative ionotropic quisqualate receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). In the absence of kainate, both quisqualate and AMPA increased [Ca2+]i though less so than did NMDA or kainate. Quisqualate (and AMPA and glutamate) were not acting as partial agonists at the kainate receptor, since the potency of these agonists in reversing the kainate [Ca2+]i response was independent of kainate concentration. Quisqualate, but not AMPA, also produced a small increase in [Ca2+]i which preceded the negative effect of this agonist on the kainate response. This increase in [Ca2+]i could also be evoked by quisqualate or glutamate after inhibition of the kainate response by AMPA. Quisqualate and glutamate, but not the other EAA agonists, also increased [Ca2+]i after chelation of extracellular calcium with EGTA. This effect appears to be mediated by the metabotropic quisqualate receptor. These cells should provide a useful system for studying regulation and interactions of EAA receptors, and for screening drugs which might act at these receptors. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/1980647/Characterization_of_Ca2_+__mobilizing_excitatory_amino_acid_receptors_in_cultured_chick_cortical_cells_ DB - PRIME DP - Unbound Medicine ER -