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Cyclothiazide acts at a site on the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor complex that does not recognize competitive or noncompetitive AMPA receptor antagonists.
J Pharmacol Exp Ther. 1995 Jan; 272(1):38-43.JP

Abstract

Activation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtype of ionotropic glutamate receptors by certain agonists, including AMPA and glutamate, has been shown to result in a rapid desensitization of the receptor. This desensitization is profoundly inhibited by the benzothiadiazide diuretic, cyclothiazide. We previously reported that cyclothiazide potentiates AMPA-induced [3H]norepinephrine ([3H]NE) release from rat hippocampal slices. We used this system to investigate the possible interaction of cyclothiazide with various AMPA receptor antagonists, including the competitive antagonist LY293558 and the 2,3-benzodiazepine noncompetitive antagonist GYKI 53655. Cyclothiazide significantly potentiated both AMPA- and KA-induced [3H]NE release from slices of the rat hippocampus. LY293558 and GYKI 53655 inhibited the potentiated and nonpotentiated AMPA- and KA-induced [3H]NE release in a concentration-dependent manner. The IC50 values for inhibition of AMPA- or KA-induced [3H]NE release by either antagonist were not affected by the presence of cyclothiazide. Thus, cyclothiazide seems to interact at a site on the AMPA receptor complex which differs from either the glutamate recognition site or the 2,3-benzodiazepine allosteric site.

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Authors+Show Affiliations

Desai MA
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.
Burnett JP
No affiliation info available
Ornstein PL
No affiliation info available
Schoepp DD
No affiliation info available

MeSH

AnimalsBenzodiazepinesBenzothiadiazinesBinding SitesBinding, CompetitiveHippocampusIn Vitro TechniquesIsoquinolinesKainic AcidMaleNorepinephrineRatsRats, Sprague-DawleyReceptors, AMPATetrazolesalpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7529311

Citation

Desai, M A., et al. "Cyclothiazide Acts at a Site On the Alpha-amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor Complex That Does Not Recognize Competitive or Noncompetitive AMPA Receptor Antagonists." The Journal of Pharmacology and Experimental Therapeutics, vol. 272, no. 1, 1995, pp. 38-43.
Desai MA, Burnett JP, Ornstein PL, et al. Cyclothiazide acts at a site on the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor complex that does not recognize competitive or noncompetitive AMPA receptor antagonists. J Pharmacol Exp Ther. 1995;272(1):38-43.
Desai, M. A., Burnett, J. P., Ornstein, P. L., & Schoepp, D. D. (1995). Cyclothiazide acts at a site on the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor complex that does not recognize competitive or noncompetitive AMPA receptor antagonists. The Journal of Pharmacology and Experimental Therapeutics, 272(1), 38-43.
Desai MA, et al. Cyclothiazide Acts at a Site On the Alpha-amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor Complex That Does Not Recognize Competitive or Noncompetitive AMPA Receptor Antagonists. J Pharmacol Exp Ther. 1995;272(1):38-43. PubMed PMID: 7529311.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cyclothiazide acts at a site on the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor complex that does not recognize competitive or noncompetitive AMPA receptor antagonists. AU - Desai,M A, AU - Burnett,J P, AU - Ornstein,P L, AU - Schoepp,D D, PY - 1995/1/1/pubmed PY - 1995/1/1/medline PY - 1995/1/1/entrez SP - 38 EP - 43 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 272 IS - 1 N2 - Activation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtype of ionotropic glutamate receptors by certain agonists, including AMPA and glutamate, has been shown to result in a rapid desensitization of the receptor. This desensitization is profoundly inhibited by the benzothiadiazide diuretic, cyclothiazide. We previously reported that cyclothiazide potentiates AMPA-induced [3H]norepinephrine ([3H]NE) release from rat hippocampal slices. We used this system to investigate the possible interaction of cyclothiazide with various AMPA receptor antagonists, including the competitive antagonist LY293558 and the 2,3-benzodiazepine noncompetitive antagonist GYKI 53655. Cyclothiazide significantly potentiated both AMPA- and KA-induced [3H]NE release from slices of the rat hippocampus. LY293558 and GYKI 53655 inhibited the potentiated and nonpotentiated AMPA- and KA-induced [3H]NE release in a concentration-dependent manner. The IC50 values for inhibition of AMPA- or KA-induced [3H]NE release by either antagonist were not affected by the presence of cyclothiazide. Thus, cyclothiazide seems to interact at a site on the AMPA receptor complex which differs from either the glutamate recognition site or the 2,3-benzodiazepine allosteric site. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/7529311/Cyclothiazide_acts_at_a_site_on_the_alpha_amino_3_hydroxy_5_methyl_4_isoxazole_propionic_acid_receptor_complex_that_does_not_recognize_competitive_or_noncompetitive_AMPA_receptor_antagonists_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7529311 DB - PRIME DP - Unbound Medicine ER -