Endogenous adenosine modulation of 22Na uptake by rat brain synaptosomes.
To evaluate if endogenous extracellular adenosine influences sodium channel activity in nerve terminals, we investigated how manipulations of extracellular adenosine levels influence 22Na uptake by rat brain synaptosomes stimulated with veratridine (VT). To decrease extracellular adenosine levels, adenosine deaminase (ADA) that converts adenosine into an inactive metabolite was used. To increase extracellular adenosine levels, we used the adenosine deaminase inhibitor erythro-9(2-hydroxy-3-nonyl) adenine (EHNA), as well as the inhibitor of adenosine transport, nitrobenzylthioinosine (NBTI). ADA (0.1-5 U/ml) caused an excitatory effect on 22Na uptake stimulated by veratridine, which was abolished in the presence of the adenosine deaminase inhibitor erythro-9(2-hydroxy-3-nonyl) adenine (EHNA, 25 microM). Both the adenosine uptake inhibitor nitrobenzylthioinosine (NBTI, 1-10 microM) and the adenosine deaminase inhibitor EHNA (10-25 microM) inhibited 22Na uptake by rat brain synaptosomes. It is suggested that adenosine is tonically inhibiting sodium uptake by rat brain synaptosomes.
Laboratory of Neurosciences, Faculty of Medicine, University of Lisbon, Portugal. Jaribeiro@neurociencias.pt
Joaquim Alexandre
JA
Ribeiro
M Graça B
MG
Lobo
Ana M
AM
Sebastião
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D012979:Sodium Radioisotopes; D013574:Synaptosomes / Q000378:metabolism*; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D058892:Adenosine Deaminase Inhibitors; D012979:Sodium Radioisotopes; D013868:Thioinosine; C010192:9-(2-hydroxy-3-nonyl)adenine; D012964:Sodium; D000243:Adenosine Deaminase; C001789:4-nitrobenzylthioinosine; D000225:Adenine; D000241:Adenosine