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Glutamate-stimulated production of inositol phosphates is mediated by Ca2+ influx in oligodendrocyte progenitors.
Eur J Pharmacol. 1997 Nov 12; 338(3):277-87.EJ

Abstract

The effect of glutamate on the accumulation of [3H]inositol phosphates was examined in oligodendrocyte progenitor cultures prepared from rat brains. Glutamate, and the analogues alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate, caused a concentration- and time-dependent increase in [3H]inositol trisphosphate (IP3) formation and the effect was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a competitive AMPA and kainate receptor antagonist. Similarly, the more selective, noncompetitive antagonist of AMPA receptors, 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466), significantly reduced the effect of both AMPA and kainate. In contrast, antagonists of N-methyl-D-aspartate (NMDA) receptor, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5, 10-imine (MK-801) and R(-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), and antagonists of metabotropic receptors, L(+)-2-amino-3-phosphono-propanoic acid (L-AP3) and alpha-methyl-4-carboxyphenylglycine (MCPG), were ineffective. These results suggest that the effect of glutamate on [3H]IP3 accumulation is mediated through ionotropic AMPA receptors. Cyclothiazide, an inhibitor of AMPA receptor desensitization, strongly potentiated the AMPA and kainate-stimulated [3H]IP3 formation as well as the uptake of 45Ca2+ in line with the previous findings. 45Ca2+ uptake evoked by AMPA or kainate, in combination with cyclothiazide, was also prevented by both CNQX and GYKI 52466. Glutamate-stimulated [3H]IP3 accumulation was prevented by EGTA, suggesting a requirement for extracellular calcium. Pre-incubation with the voltage-gated Ca2+ channel blockers, diltiazem, nifedipine and CdCl2, partially prevented the glutamate-induced [3H]IP3 accumulation as well as 45Ca2+ uptake. Similarly, the Na+/Ca2+ exchanger blockers benzamil and 3,4-dichlorobenzamil reduced significantly kainate-stimulated 45Ca2+ uptake. These data indicate that glutamate-induced [3H]IP3 accumulation is triggered by calcium influx via AMPA receptors, voltage-gated calcium channels and the Na+/Ca2+ exchanger operating in reverse mode.

Authors+Show Affiliations

Department of Pharmacology and Therapeutics, McGill University, Montreal, Que., Canada.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

9424022

Citation

Liu, H N., et al. "Glutamate-stimulated Production of Inositol Phosphates Is Mediated By Ca2+ Influx in Oligodendrocyte Progenitors." European Journal of Pharmacology, vol. 338, no. 3, 1997, pp. 277-87.
Liu HN, Molina-Holgado E, Almazan G. Glutamate-stimulated production of inositol phosphates is mediated by Ca2+ influx in oligodendrocyte progenitors. Eur J Pharmacol. 1997;338(3):277-87.
Liu, H. N., Molina-Holgado, E., & Almazan, G. (1997). Glutamate-stimulated production of inositol phosphates is mediated by Ca2+ influx in oligodendrocyte progenitors. European Journal of Pharmacology, 338(3), 277-87.
Liu HN, Molina-Holgado E, Almazan G. Glutamate-stimulated Production of Inositol Phosphates Is Mediated By Ca2+ Influx in Oligodendrocyte Progenitors. Eur J Pharmacol. 1997 Nov 12;338(3):277-87. PubMed PMID: 9424022.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glutamate-stimulated production of inositol phosphates is mediated by Ca2+ influx in oligodendrocyte progenitors. AU - Liu,H N, AU - Molina-Holgado,E, AU - Almazan,G, PY - 1998/1/10/pubmed PY - 1998/1/10/medline PY - 1998/1/10/entrez SP - 277 EP - 87 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 338 IS - 3 N2 - The effect of glutamate on the accumulation of [3H]inositol phosphates was examined in oligodendrocyte progenitor cultures prepared from rat brains. Glutamate, and the analogues alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate, caused a concentration- and time-dependent increase in [3H]inositol trisphosphate (IP3) formation and the effect was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a competitive AMPA and kainate receptor antagonist. Similarly, the more selective, noncompetitive antagonist of AMPA receptors, 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466), significantly reduced the effect of both AMPA and kainate. In contrast, antagonists of N-methyl-D-aspartate (NMDA) receptor, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5, 10-imine (MK-801) and R(-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), and antagonists of metabotropic receptors, L(+)-2-amino-3-phosphono-propanoic acid (L-AP3) and alpha-methyl-4-carboxyphenylglycine (MCPG), were ineffective. These results suggest that the effect of glutamate on [3H]IP3 accumulation is mediated through ionotropic AMPA receptors. Cyclothiazide, an inhibitor of AMPA receptor desensitization, strongly potentiated the AMPA and kainate-stimulated [3H]IP3 formation as well as the uptake of 45Ca2+ in line with the previous findings. 45Ca2+ uptake evoked by AMPA or kainate, in combination with cyclothiazide, was also prevented by both CNQX and GYKI 52466. Glutamate-stimulated [3H]IP3 accumulation was prevented by EGTA, suggesting a requirement for extracellular calcium. Pre-incubation with the voltage-gated Ca2+ channel blockers, diltiazem, nifedipine and CdCl2, partially prevented the glutamate-induced [3H]IP3 accumulation as well as 45Ca2+ uptake. Similarly, the Na+/Ca2+ exchanger blockers benzamil and 3,4-dichlorobenzamil reduced significantly kainate-stimulated 45Ca2+ uptake. These data indicate that glutamate-induced [3H]IP3 accumulation is triggered by calcium influx via AMPA receptors, voltage-gated calcium channels and the Na+/Ca2+ exchanger operating in reverse mode. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/9424022/Glutamate_stimulated_production_of_inositol_phosphates_is_mediated_by_Ca2+_influx_in_oligodendrocyte_progenitors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(97)81931-0 DB - PRIME DP - Unbound Medicine ER -