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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Laudadio, M. A.
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Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών και Τεχνολογιών. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιών
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Laudadio, M. A.
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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.
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