A paradoxical inhibitory effect of xanthines on hippocampal excitability in calcium-free media.
In calcium-free media, neurones in the rat hippocampal slice develop bursts of population potentials and lose their sensitivity to adenosine. The present paper reports the unexpected and paradoxical finding that the xanthines theophylline and cyclopentyltheophylline, the latter of which is selective for A1 purine receptors, depressed the excitability of hippocampal pyramidal neurones in calcium-free media. Chelating residual calcium with EGTA reduced excitability which was additive with the xanthine effect, while 100 microM calcium depressed the response to theophylline. The inhibition by xanthines was prevented by adenosine, which had no effect by itself, but was not reproduced or modified by adenosine deaminase. The xanthine effects were also prevented by baclofen and carbamazepine. A common feature of adenosine, baclofen and carbamazepine which may account for their antagonism of the xanthines is the blockade of calcium fluxes. It is proposed that in the presence of low external concentrations of calcium xanthines can reduce excitability by promoting the mobilisation and trans-membrane movement of residual calcium in the medium or neuronal membranes.
Hosseinzadeh
H
H
Department of Pharmacology, University of Glasgow, UK.
Stone
T W
TW
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002220:Carbamazepine / Q000494:pharmacology; D003470:Culture Media; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
D003470:Culture Media; D014970:Xanthines; D002220:Carbamazepine; D013806:Theophylline; D001418:Baclofen; D000241:Adenosine; D002118:Calcium