Changes in nucleotide hydrolysis in rat blood serum induced by pentylenetetrazol-kindling.
There is growing pharmacological evidence from several animal models of seizure disorders that adenosine possesses endogenous anticonvulsant activity. Apart from being released from cells, adenosine can be produced by the degradation of adenine nucleotides by ectoenzymes or soluble nucleotidases. These enzymes constitute an important mechanism in synaptic modulation, as they hydrolyze ATP, an excitatory neurotransmitter, to adenosine, a neuroprotective compound. We recently demonstrated an increase in ectoenzyme activity in rat brain synaptosomes after pentylenetetrazol-kindling in rats resistant to kindling, suggesting a role for ectonucleotidases in the seizure control. The present work investigates the effect of seizures induced by pentylenetetrazol kindling on the enzymes that could be playing a role in ATP, ADP and AMP hydrolysis to adenosine in rat blood serum. Animals received injections of PTZ (30 mg/kg, i.p., dissolved in 0.9% saline) once every 48 h, totaling 10 stimulations and the controls animals were injected with saline. The hydrolysis of ATP, ADP and AMP were significantly increased (42, 40, and 45%, respectively), while phosphodiesterase activity was unchanged. These results suggest once more that an increase in the ATP diphosphohydrolase and 5'-nucleotidase activities and, possibly, in adenosine levels, could represent an important compensatory mechanism in the development of chronic epilepsy. Moreover, the fact that this increase can also be measured in serum could mean that these enzymes might be useful as plasma markers of seizures in epilepsy.
Bruno
Alessandra Nejar
AN
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 2600-ANEXO, 90035-003 Porto Alegre, RS, Brazil.
Oses
Jean Pierre
JP
Amaral
Olavo
O
Coitinho
Adriana
A
Bonan
Carla Denise
CD
Battastini
Ana Maria Oliveira
AM
Sarkis
João José Freitas
JJ
D015720:5'-Nucleotidase / Q000187:drug effects / Q000378:metabolism; D000227:Adenine Nucleotides / Q000378:metabolism*; D000241:Adenosine / Q000096:biosynthesis*; D000818:Animals; D001081:Apyrase / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000097:blood* / Q000139:chemically induced / Q000201:enzymology*; D005260:Female; D006868:Hydrolysis / Q000187:drug effects; D007696:Kindling, Neurologic / Q000378:metabolism*; D009708:Nucleotidases / Q000097:blood*; D010433:Pentylenetetrazole / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000227:Adenine Nucleotides; D015415:Biomarkers; D003292:Convulsants; D009708:Nucleotidases; D015720:5'-Nucleotidase; D001081:Apyrase; D000241:Adenosine; D010433:Pentylenetetrazole