The A3 adenosine receptor agonist 2-Cl-IB-MECA facilitates epileptiform discharges in the CA3 area of immature rat hippocampal slices.
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 microM). Evoked potentials: 2-Cl-IB-MECA (1-50 microM, n = 17) had consistently excitatory effects, blocked by the A(3) receptor antagonist MRS 1220 (1 microM, n = 7), but not occluded in the presence of the A(1) antagonist DPCPX (1 microM, n = 12) or the A(2A) antagonist ZM-241385 (0.1 microM, n = 12). 2-Cl-IB-MECA reversed the inhibitory effects (n = 5) of the adenosine uptake blocker nitrobenzylthioinosine (NBTI, 50 microM), but did not increase its excitatory effects (n = 19). Spontaneous discharges: 2-Cl-IB-MECA (1 microM) 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 A(3) receptors. In conclusion, these findings suggest strongly that activation of A(3) 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.
Laudadio
Mark Anthony
MA
Department of Paediatrics, Ste-Justine Hospital Research Centre, Université de Montréal, 3175 Côte-Ste-Catherine, Montreal, Que., Canada H3T 1C5.
Psarropoulou
Caterina
C
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D058909:Adenosine A3 Receptor Agonists; D000818:Animals; D000831:Animals, Newborn; D004827:Epilepsy / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D043684:Receptor, Adenosine A3 / Q000378:metabolism
D058909:Adenosine A3 Receptor Agonists; D043684:Receptor, Adenosine A3; D000241:Adenosine; C090034:2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide