title: Pentylenetetrazol kindling alters adenine and guanine nucleotide catabolism in rat hippocampal slices and cerebrospinal fluid.
abstract: 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.
authors.affiliation: 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
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Oses
authors.forename: Giordano Gubert
authors.initials: GG
authors.lastname: Viola
authors.forename: Giana
authors.initials: G
authors.lastname: de Paula Cognato
authors.forename: Victor Hermes Cereser
authors.initials: VH
authors.lastname: Júnior
authors.forename: Gisele
authors.initials: G
authors.lastname: Hansel
authors.forename: Ana Elisa
authors.initials: AE
authors.lastname: Böhmer
authors.forename: Renata
authors.initials: R
authors.lastname: Leke
authors.forename: Alessandra Nejar
authors.initials: AN
authors.lastname: Bruno
authors.forename: Carla Denise
authors.initials: CD
authors.lastname: Bonan
authors.forename: Maurício Reis
authors.initials: MR
authors.lastname: Bogo
authors.forename: Luis Valmor
authors.initials: LV
authors.lastname: Portela
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
authors.forename: João José Freitas
authors.initials: JJ
authors.lastname: Sarkis
mesh_terms: 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
chemical_list: D000227:Adenine Nucleotides; D003292:Convulsants; D006150:Guanine Nucleotides; D009419:Nerve Tissue Proteins; D011687:Purines; D009708:Nucleotidases; D015720:5'-Nucleotidase; D010433:Pentylenetetrazole