The nucleoside-transport inhibitor soluflazine (R 64 719) increases the effects of adenosine in the guinea-pig hippocampal slice and is antagonized by adenosine deaminase.
Field EPSP slope and population spike (PS) amplitude were measured in the CA1 pyramidal cell region after double-pulse stimulation of the striatum radiatum in hippocampal slices of guinea-pig. Iontophoresis of adenosine reduced the EPSP slope to 77.9 +/- 5.0% (mean +/- S.E.M.) and PS amplitude to 32.9 +/- 9.7% of the control values. Recovery was 98.7 +/- 3% for the EPSP and 82.9 +/- 7.0% for the PS 1.5 min after iontophoresis was stopped. In the presence of soluflazine 10(-6) M the effects of adenosine iontophoresis on the PS amplitude were significantly increased and the recovery of the EPSP and PS was significantly delayed. Soluflazine perfusion alone gradually decreased EPSP slope and PS amplitude as with adenosine. The reductions in EPSP slope and PS amplitude produced by soluflazine were antagonized by adenosine deaminase. An increase in EPSP slope and PS amplitude was seen when adenosine deaminase was given first. This increase was not reduced by exposure to soluflazine. These results are compatible with the hypothesis that soluflazine acts as a nucleoside transport inhibitor in the CNS, where it may increase the extracellular concentration of adenosine.
Ashton
D
D
Department of Neuropharmacology, Janssen Pharmaceutica Research Laboratories, Beerse, Belgium.
Willems
R
R
De Prins
E
E
Van Belle
H
H
Wauquier
A
A
D000241:Adenosine / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D004558:Electric Stimulation; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D066298:In Vitro Techniques; D007478:Iontophoresis; D008297:Male; D009700:Nucleoside Deaminases / Q000494:pharmacology*; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D010879:Piperazines; C054695:soluflazine; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D000241:Adenosine