Pentylenetetrazol kindling alters adenine and guanine nucleotide catabolism in rat hippocampal slices and cerebrospinal fluid.
Pentylenetetrazol (PTZ) is commonly used as a convulsant drug. The enhanced seizure susceptibility induced by kindling is probably attributable to plastic changes in the synaptic efficacy. Adenosine and guanosine act both as important neuromodulators and neuroprotectors with mostly inhibitory effects on neuronal activity. Adenosine and guanosine can be released per se or generated from released nucleotides (ATP, ADP, AMP, GTP, GDP, and GMP) that are metabolized and rapidly converted to adenosine and guanosine. The aim of this study was to evaluate nucleotide hydrolysis by ecto- and soluble nucleotidases (hippocampal slices and CSF, respectively) after PTZ-kindling (stages 3, 4, or 5 seizures) or saline treatment in rats. Additionally, the levels of purines in rat cerebrospinal fluid (CSF), as well as ecto-NTPDases (1, 2, 3, 5, 6 and 8) and ecto- 5'-nucleotidase expression were determined. Ecto-enzyme assays demonstrated that ATP, AMP, GDP, and GMP hydrolysis enhanced when compared with controls. In addition, there was an increase of ADP, GDP, and GMP hydrolysis by soluble nucleotidases in PTZ-kindling rats compared to control group. The HPLC analysis showed a marked increase in PTZ-kindled CSF concentrations of GTP, ADP, and uric acid, but GDP, AMP, and hypoxanthine concentrations were decreased. Such alterations indicate that the modulatory role of purines in CNS could be affected by PTZ-kindling. However, the physiological significance of these findings remains to be elucidated.
Oses
Jean Pierre
JP
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul. Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003 Porto Alegre, RS, Brazil. jean.pierre.oses@gmail.com
Viola
Giordano Gubert
GG
de Paula Cognato
Giana
G
Júnior
Victor Hermes Cereser
VH
Hansel
Gisele
G
Böhmer
Ana Elisa
AE
Leke
Renata
R
Bruno
Alessandra Nejar
AN
Bonan
Carla Denise
CD
Bogo
Maurício Reis
MR
Portela
Luis Valmor
LV
Souza
Diogo Onofre
DO
Sarkis
João José Freitas
JJ
D015720:5'-Nucleotidase / Q000096:biosynthesis; D000227:Adenine Nucleotides / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003292:Convulsants; D005260:Female; D006150:Guanine Nucleotides / Q000134:cerebrospinal fluid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006868:Hydrolysis; D007696:Kindling, Neurologic / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009708:Nucleotidases / Q000378:metabolism; D010433:Pentylenetetrazole; D011687:Purines / Q000134:cerebrospinal fluid; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000227:Adenine Nucleotides; D003292:Convulsants; D006150:Guanine Nucleotides; D009419:Nerve Tissue Proteins; D011687:Purines; D009708:Nucleotidases; D015720:5'-Nucleotidase; D010433:Pentylenetetrazole