Epileptogenic actions of xanthines in relation to their affinities for adenosine A1 receptors in CA3 neurons of hippocampal slices (guinea pig).
In order to analyze the epileptogenic mechanisms of caffeine and related xanthines, putative effects of these drugs were studied on adenosine receptors of CA3 neurons in hippocampal slices. Epileptogenic concentrations of different xanthine derivatives strongly correlated with their affinities for the inhibitory A1 adenosine receptor subtype. The A1 receptor agonists adenosine and R-PIA reversibly depressed xanthine-induced epileptic activity without effects on the resting membrane potential or on spontaneously occurring action potentials. These findings suggest that the epileptogenic potency of xanthines is primarily due to the blockade of the A1 receptors through an abnormal rise of intracellular cAMP and to the excessive transmembrane calcium fluxes underlying paroxysmal depolarization shifts.
Moraidis
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I
Institut für Physiologie, IG1, Essen, FRG.
Bingmann
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D
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D014970:Xanthines / Q000493:pharmacokinetics* / Q000494:pharmacology*
D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; D010660:Phenylisopropyladenosine; D002110:Caffeine; D000242:Cyclic AMP; D008274:Magnesium; D000241:Adenosine; D002118:Calcium