Carbamazepine inhibits the potentiation by adenosine analogues of agonist induced inositolphosphate formation in hippocampal astrocyte cultures.
Carbamazepine (CBZ) resembles lithium in its beneficial effects in therapy and prophylaxis of affective disorders. Since lithium is presumed to act via an attenuation of the inositolphosphate/Ca(2+)-second messenger system, it is of particular interest whether or not CBZ might also have inhibitory effects on this type of signal transduction. CBZ is an antagonist of adenosine A1-receptor subtypes. We show here that activation of adenosine A1-receptors potentiates the phenylephrine induced formation of inositolphosphates in hippocampal astrocytes and that this potentiating effect is inhibited by CBZ at a therapeutically relevant concentration. These results indicate that CBZ can by antagonism of adenosine A1-receptors inhibit the inositolphosphate/Ca(2+)-signalling in neural pathways regulated by adenosine.
Biber
K
K
Department of Psychiatry, University of Freiburg, Germany.
Walden
J
J
Gebicke-Härter
P
P
Berger
M
M
van Calker
D
D
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects*; D002220:Carbamazepine / Q000494:pharmacology*; D002478:Cells, Cultured; D004357:Drug Synergism; D006624:Hippocampus / Q000187:drug effects*; D007295:Inositol Phosphates / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000145:classification; D015290:Second Messenger Systems / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D007295:Inositol Phosphates; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D010656:Phenylephrine; C045537:inositol 4-phosphate; D002220:Carbamazepine; D018021:Lithium Chloride; D000241:Adenosine