ISSN:
1460-9568
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
The purine nucleoside adenosine is released during seizure activity and exerts an anticonvulsant influence through inhibition of glutamate release and hyperpolarization of neurons via adenosine A1 receptors. However, activation of adenosine A2A and A3 receptors may counteract the inhibitory effects of A1 receptors. We have therefore examined the extent to which endogenous adenosine released during seizure activity activates the different adenosine receptor subtypes and the implications for seizure activity in the rat hippocampus in vitro. Brief trains of high-frequency stimulation in nominally Mg2+-free artificial cerebrospinal fluid evoked epileptiform activity and resulted in a transient depression of the simultaneously recorded CA1 field excitatory postsynaptic potential. In the presence of 8-cyclopentyl-1,3-dimethylxanthine (CPT), an adenosine A1 receptor antagonist, the occurrence of spontaneous seizure activity was greatly increased as was the duration and intensity of evoked seizures, whilst the postictal depression of basal synaptic transmission was greatly attenuated. Application of ZM 241385, an adenosine A2A receptor antagonist, shortened the duration of epileptiform activity, whereas administration of MRS 1191, an adenosine A3 receptor antagonist, both decreased the duration and intensity of seizures. Combined application of the A2A and A3 receptor antagonists also resulted in a reduction in seizure duration and intensity. However, no evidence was found for a role for protein kinase C in the regulation of seizure activity by endogenous adenosine. Our data confirm the dominant anticonvulsant role that endogenous and tonic adenosine play via the A1 receptor, and suggest that the additional adenosine receptor subtypes may compromise this anticonvulsant property through promotion of seizure activity.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.0953-816X.2004.03355.x
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