Effects of suramin on hippocampal apyrase activity and inhibitory avoidance learning of rats.
The action of suramin on apyrase activity in hippocampal synaptosomes and its effects on retention of inhibitory avoidance learning were evaluated. Suramin, a P2-purinoceptor antagonist, significantly inhibited in a noncompetitive manner the ATP and ADP hydrolysis promoted by apyrase in hippocampal synaptosomes of adult rats. The Ki values obtained were 72.8 and 109 microM for ATP and ADP hydrolysis, respectively. Intrahippocampal infusion of suramin (0.01, 0.1, 1, and 10 microg) immediately posttraining, in a dose-dependent effect, significantly reduced the response latency during the retention test applied 24 h after the rats received step-down inhibitory avoidance training. The amnesic effects promoted by suramin probably occur by its antagonist action on hippocampal P2-purinoceptors and NMDA receptors. In view of the fact that ATP-metabolizing enzymes and P2-purinoceptors have similar binding domains, these results suggest that suramin can either alter ATP degradation and/or block purinergic neurotransmission.
Bonan
C D
CD
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Roesler
R
R
Quevedo
J
J
Battastini
A M
AM
Izquierdo
I
I
Sarkis
J J
JJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001081:Apyrase / Q000378:metabolism*; D001362:Avoidance Learning / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D006868:Hydrolysis; D008297:Male; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D013498:Suramin / Q000494:pharmacology*
D058919:Purinergic P2 Receptor Antagonists; D013498:Suramin; D000255:Adenosine Triphosphate; D001081:Apyrase