Striatum adenosine A2 receptors are modified during seizure: effect of cyclopentyladenosine administration.
Rat CNS adenosine A2A receptors were studied after administration of the convulsant drug 3-mercaptopropionic acid (MP) and the adenosine analogue cyclopentyladenosine (CPA) by means of a quantitative autoradiographic method. Specific binding was quantified in striatum only. The highest density was found in caudate-putamen (2.50 fmol/mm2), followed by nuclei accumbens (1.85 fmol/mm2) and the lowest values in the olfactory tubercle (1.26 fmol/mm2). These differences were statistically significant. MP administration (150 mg/kg) caused significant increases (12-18%) in caudate-putamen and nuclei accumbens in both stages: seizure and postseizure and no changes in the olfactory tubercle. CPA administration (2 mg/kg) originated a rise of 16% in nuclei accumbens but no change in the other two regions. When CPA was injected 30 minutes before MP, an increase (18 to 45%) in caudate-putamen and nuclei accumbens at seizure and postseizure stages was observed. Saturation results, in striatal membrane fraction, indicate that receptor sites increased their maximal binding capacity (Bmax) while the apparent dissociation constant (Kd) remained unchanged. These results suggest the involvement of the adenosine A2A receptors in convulsant activity and that CPA administration at the dose selected brings about a rise in neuronal excitability in this area.
Giraldez
L
L
Instituto de Biología Celular y de Neurociencia Prof Eduardo De Robertis, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Zanetti
F
F
Girardi
E
E
D015097:3-Mercaptopropionic Acid / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D003292:Convulsants / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*
D003292:Convulsants; C048599:N(6)-cyclopentyladenosine; D015097:3-Mercaptopropionic Acid; D000241:Adenosine