Is the sigma 2 receptor in rat brain related to the K+ channel of class III antiarrhythmic drugs?
The sigma 2 receptor subtype was studied in rat cerebral cortex and in C6 glioma cells homogenates using various compounds including class III antiarrhythmic drugs. The characteristics of (+)-[3H]-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-[3H]-3-PPP) binding were assessed in competition experiments with different displacers which revealed the presence of sigma 2 receptors. Various class III antiarrhythmic drugs inhibited (+)-[3H]-3-PPP binding with high affinity and their binding affinity was found to correlate with the potency of these compounds to increase the duration of action potentials measured in Purkinje fibers in electrophysiological studies. Since class III antiarrhythmic drugs are known to interact with voltage-dependent K+ channels, the present results provide evidence that the (+)-[3H]-3-PPP binding sites in rat brain possess the characteristics of K+ channels of class III antiarrhythmic drugs.
Jeanjean
A P
AP
Laboratoire de Neurochimie, Université Catholique de Louvain, Brussels, Belgium.
Mestre
M
M
Maloteaux
J M
JM
Laduron
P M
PM
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism; D004594:Electrophysiology; D005910:Glioma / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010880:Piperidines / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*; D011690:Purkinje Fibers / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D015259:Dopamine Agents; D010880:Piperidines; D015221:Potassium Channels; D017480:Receptors, sigma; C026539:preclamol