Effect of A_2A adenosine receptor stimulation and antagonism on synaptic depression induced by in vitro ischaemia in rat hippocampal slices

Abstract

1 In the present study we investigated the role of A 2A adenosine receptors in hippocampal synaptic transmission under in vitro ischaemia-like conditions. 2 The e ects of adenosine, of the selective A 2A receptor agonist, CGS 21680 (2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamidoadenosine), and of selective A 2A receptor antagonists, ZM 241385 (4-(2-[7-amino-2-(2-furyl)-{1,2,4}-triazolo{2,3-a}{1,3,5}triazin-5-ylamino]ethyl)phenol) and SCH 58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine), have been evaluated on the depression of ®eld e.p.s.ps induced by an in vitro ischaemic episode. 3 The application of 2 min of in vitro ischaemia brought about a rapid and reversible depression of ®eld e.p.s.ps, which was completely prevented in the presence of the A 1 receptor antagonist DPCPX (1,3-dipropyl-8-cyclopentylxanthine) (100 nM). On the other hand both A 2A receptor antagonists, ZM 241385 and SCH 58261, by themselves did not modify the ®eld e.p.s.ps depression induced by in vitro ischaemia. 4 A prolonged application of either adenosine (100 mM) or CGS 21680 (30, 100 nM) before the in vitro ischaemic episode, signi®cantly reduced the synaptic depression. These e ects were antagonized in the presence of ZM 241385 (100 nM). 5 SCH 58261 (1 and 50 nM) did not antagonize the e ect of 30 nM CGS 21680 on the ischaemiainduced depression. 6 These results indicate that in the CA1 area of the hippocampus the stimulation of A 2A adenosine receptors attenuates the A 1 -mediated depression of synaptic transmission induced by in vitro ischaemia.

Role of adenosine A3 receptors on CA1 hippocampal neurotransmission during oxygen–glucose deprivation episodes of different duration

“…3 show that periods of 2-or 5-min OGD induced, respectively, a partial or complete reduction of synaptic potential amplitude that was always reversible upon reperfusion with normal oxygenated aCSF. These results are in agreement with our previous studies [13,27,28].…”

“…A decrease in fEPSP depression, brought about by A 3 agonists, hypothetically might be attributed to A 2A receptor stimulation. It was, in fact, previously demonstrated that selective stimulation of A 2A receptors by CGS 21680 decreases fEPSP depression induced by 2-min OGD and that the effect is antagonized by the selective A 2A antagonist ZM 241385 [28]. However, the concentration of Cl-IB-MECA used in the present study (10 nM) is highly selective for A 3 versus A 2A receptors [32], and the effect of Cl-IB-MECA is not antagonized by ZM 241385, indicating that Cl-IB-MECA-induced depression of fEPSP inhibition during 2-min OGD is not mediated by A 2A adenosine receptors.…”

“…Unlike prolonged (7-min) OGD, depression of synaptic responses caused by OGD episodes of short duration (2 or 5 min) is fully reversible [13,27,28] and is not sufficient to trigger AD. The decrease in fEPSP depression or the faster recovery of fEPSP amplitude during the selective block of A 3 receptors indicates an inhibitory role of A 3 receptors on synaptic transmission during brief OGD.…”

“…The decrease in fEPSP depression or the faster recovery of fEPSP amplitude during the selective block of A 3 receptors indicates an inhibitory role of A 3 receptors on synaptic transmission during brief OGD. We previously demonstrated that depression of synaptic potentials during 2-or 5-min OGD is almost completely antagonized in the presence of the selective A 1 adenosine receptor antagonist DPCPX [10,27,28]. Most of the known neuroprotective effects of adenosine during ischemia both in vivo and in vitro are attributed to the depression of synaptic activity induced by the activation of A 1 receptors.…”

“…Prolonged, severe episodes of OGD bring about the irreversible depression of neurotransmission and the appearance of AD [14,25], a phenomenon strictly correlated with the extent of brain damage during ischemia both in vivo and in vitro [26]. Brief periods of ischemia are followed by complete recovery of neurotransmission and imply shorter times of A 3 receptor stimulation by endogenous adenosine released during the ischemic episode [10,13,27,28].…”