Long-term effect of convulsive behavior on the density of adenosine A1 and A 2A receptors in the rat cerebral cortex.
OBJECTIVE
Adenosine is a neuromodulator that has been proposed to act as an anticonvulsant mainly via inhibitory A1 receptors, but recent data show that genetic deletion of facilitatory A 2A receptors might also attenuate convulsions. Since both A1 and A 2A receptors are prone to down- and upregulation in different stressful situations, we investigated if convulsive behavior leads to a long-term change in A1 and A 2A receptor density in the rat cerebral cortex.


METHODS
Stage 4-5 convulsions (Racine's scale) were induced in adult Wistar rats either through amygdala stimulation (kindling) or by intraperitoneal injection of kainate (10 mg/ml). Rats were killed after 4 weeks to evaluate adenosine A1 and A 2A receptor density in the cerebral cortex using both Western blot and membrane binding assays.


RESULTS
The binding density of the A1 antagonist, 3H-DPCPX, decreased by 40. +/- 4.4% and by 20.7 +/- 0.5% after kindling or kainate injection. Likewise, A1 receptor immunoreactivity in cortical membranes from kindled or kainate-injected rats decreased by 19.1 +/- 3.3% and 12.7 +/- 5.7%, respectively. In contrast, the binding density of the A 2A receptor antagonist 3H-SCH 58261 increased by 293 +/- 34% and by 159 +/- 32% in cortical membranes from kindled or kainate-injected rats, and A 2A receptor immunoreactivity also increased by 151 +/- 12% and 79.6 +/- 7.0%.


CONCLUSIONS
This indicates that after convulsive behavior there is a long-term decrease of A1 receptors accompanied by an increased density of A 2A receptors, suggesting that A 2A antagonists rather than A1 agonists may be more promising anticonvulsive drugs.
Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Nelson
N
Rebola
Lisiane O
LO
Porciúncula
Luísa V
LV
Lopes
Catarina R
CR
Oliveira
Patrício
P
Soares-da-Silva
Rodrigo A
RA
Cunha
D000679:Amygdala / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000737:chemistry*; D015536:Down-Regulation / Q000502:physiology; D004558:Electric Stimulation; D007608:Kainic Acid; D007696:Kindling, Neurologic / Q000502:physiology; D008297:Male; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism*; D013995:Time; D015854:Up-Regulation / Q000502:physiology; D014970:Xanthines / Q000378:metabolism / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D007608:Kainic Acid