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2-pyrrolidinone induces a long-lasting facilitation of hippocampal synaptic transmission by enhancing alpha7 ACh receptor responses via a PKC pathway.

Authors :
Miyamoto H
Yaguchi T
Ohta K
Nagai K
Nagata T
Yamamoto S
Nishizaki T
Source :
Brain research. Molecular brain research [Brain Res Mol Brain Res] 2003 Sep 10; Vol. 117 (1), pp. 91-6.
Publication Year :
2003

Abstract

2-Pyrrolidinone, a metabolite of aniracetam, potentiated currents through alpha7 receptors expressed in Xenopus oocytes, in a bell-shaped dose-dependent manner at concentrations ranged from 1 nM to 10 microM, with a maximum at 100 nM (189% of original levels 60 min after 20-min treatment). The potentiation was inhibited by GF109203X, a selective inhibitor of protein kinase C (PKC), but not by KN-93, a selective inhibitor of CaMKII, or H-89, a selective inhibitor of protein kinase A (PKA). In the PKC assay using reversed-phase high-performance liquid chromatography, 2-pyrrolidinone enhanced activity of PKC-epsilon activated by linoleic acid to about 1.8-times greater than that in the absence of 2-pyrrolidinone, although it did not directly activate PKC-epsilon. In the Western immunoblot analysis, rat hippocampal slices treated with 2-pyrrolidinone (100 nM) was more reactive to an antibody against phosphorylated myristoylated alanine-rich C kinase substrate (MARCKS) than untreated slices. 2-Pyrrolidinone (100 nM) induced a long-lasting facilitation of hippocampal synaptic transmission in the CA1 region of rat hippocampal slices, and the facilitation was inhibited by GF109203X or alpha-bungarotoxin, an inhibitor of alpha7 receptors. The results of the present study suggest that 2-pyrrolidinone enhances activity of activated PKC, thereby potentiating alpha7 receptor responses, and then leading to a facilitation of hippocampal synaptic transmission.

Details

Language :
English
ISSN :
0169-328X
Volume :
117
Issue :
1
Database :
MEDLINE
Journal :
Brain research. Molecular brain research
Publication Type :
Academic Journal
Accession number :
14499485
Full Text :
https://doi.org/10.1016/s0169-328x(03)00281-x