The A(3) adenosine receptor agonist 2-Cl-IB-MECA facilitates epileptiform discharges in the CA(3) area of immature rat hippocampal slices

 
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2004 (EN)
The A(3) adenosine receptor agonist 2-Cl-IB-MECA facilitates epileptiform discharges in the CA(3) area of immature rat hippocampal slices (EN)

Laudadio, M. A. (EN)

Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών και Τεχνολογιών. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιών (EL)
Laudadio, M. A. (EN)

The effects of the A(3) adenosine receptor agonist 2-Cl-IB-MECA were tested on epileptiform field potentials recorded in the CA3 area of postnatal days 10-20 immature hippocampal slices, during perfusion with the GABA(A) receptor antagonist bicuculline (10 muM). Evoked potentials: 2-Cl-IB-MECA (1-50 muM, n = 17) had consistently excitatory effects, blocked by the A3 receptor antagonist MRS 1220 (1 muM, n = 7), but not occluded in the presence of the A(1) antagonist DPCPX (1 muM, n = 12) or the A(2A) antagonist ZM-241385 (0.1 muM, n = 12). 2-Cl-IB-MECA reversed the inhibitory effects (n = 5) of the adenosine uptake blocker nitrobenzylthioinosine (NBTI, 50 muM), but did not increase its excitatory effects (n = 19). Spontaneous discharges: 2-Cl-113-MECA (1 muM) induced them or increased their frequency in 14/30 slices, an effect reversed by MRS 1220 (n = 3), and observed also following pre-perfusion with DPCPX (n = 11), ZM-241385 (n = 11) or both (n = 10). In the presence of the A(1) antagonist DPCPX, NBTI increased the frequency of spontaneous discharges, an effect partially reversed by MRS 1220 (n = 8), thus suggesting that a rise in endogenous adenosine during disinhibition may activate A3 receptors. In conclusion, these findings suggest strongly that activation of A3 receptors, following a rise in endogenous adenosine (i.e. during seizures, hypoxia), facilitates excitation, thus limiting the known inhibitory and/or neuroprotective effects of adenosine in immature brain. (C) 2004 Elsevier B.V. All rights reserved. (EN)

purinergic (EN)

Πανεπιστήμιο Ιωαννίνων (EL)
University of Ioannina (EN)

Epilepsy Res (EN)

English

2004

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