Kinazolon-alkil-karbonsav származékok hatása az α-amino-3-hidroxi-5-metil-4-izoxazol propionsav (AMPA) receptor által szabályozott transzmembrán Ca2+ ion fluxusra

Translated title of the contribution: Effect of quinazolon-alkyl-carboxylic acid derivatives on the transmembrane Ca2+ ion flux mediated by AMPA receptors

E. Szárics, Lasztóczi Bálint, L. Nyikos, Barabás Péter, Kovács Ilona, Skuban Nina, Péter I. Nagy, J. Kökösi, K. Takács-Novák, J. Kardos

Research output: Contribution to journalArticle

Abstract

The excitatory neurotransmitter, Glu, plays a crucial role in many sensory and motor functions as well as in brain development, learning and memory and it is also involved in the pathogenesis of a number of neurological disorders, including epilepsy, Alzheimer's and Parkinson's diseases. Therefore, the study of Glu receptors (GluRs) is of therapeutical importance. We showed here by fluorescence monitoring of transmembrane Ca2+ ion fluxes in response to (S)-α-amino-3-hidroxi-5-metil-4-izoxazol propionic acid ((S)-AMPA) on the time scale of 0.00004-10 s that Ca2+ ion influx proceeds through faster and slower desensitizing receptors. Pharmacological isolation of the slower and faster desensitizing AMPA receptor was possible by fluorescence monitoring of Ca2+ ion translocation in response to (S)-AMPA in the presence and absence of various 2-methyl-4-oxo-3H-quinazoline-3-alkyl-carboxilic acid derivatives (Qxs): the acetic acid Q1 inhibits the slower desensitizing receptor response specifically, while the acetyl-piperidine Q5 is a more potent inhibitor of the faster desensitizing receptor response. In addition, spontaneous interictal activity, as induced by high [K+] conditions in hippocampal slices, was reduced significantly by Q5, suggesting a possible anticonvulsant property of Q5. Substitutions of Qxs into the GluR2 S1S2 binding core were consistent with their effect by causing variable degree of S1S2 bridging interaction as one of the main determinants of AMPA receptor agonist activity. The exploitation of differences between similar receptors will be important in the development and use of drugs with high pharmacological specificity.

Original languageHungarian
Pages (from-to)116-122
Number of pages7
JournalActa Pharmaceutica Hungarica
Volume72
Issue number2
Publication statusPublished - 2002

Fingerprint

AMPA Receptors
Carboxylic Acids
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Ions
Fluorescence
Pharmacology
Quinazolines
Nervous System Diseases
Acetic Acid
Anticonvulsants
Neurotransmitter Agents
Parkinson Disease
Epilepsy
Alzheimer Disease
Learning
Acids
Brain
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Kinazolon-alkil-karbonsav származékok hatása az α-amino-3-hidroxi-5-metil-4-izoxazol propionsav (AMPA) receptor által szabályozott transzmembrán Ca2+ ion fluxusra. / Szárics, E.; Bálint, Lasztóczi; Nyikos, L.; Péter, Barabás; Ilona, Kovács; Nina, Skuban; Nagy, Péter I.; Kökösi, J.; Takács-Novák, K.; Kardos, J.

In: Acta Pharmaceutica Hungarica, Vol. 72, No. 2, 2002, p. 116-122.

Research output: Contribution to journalArticle

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