GABAB-receptor mediated inhibition of potassium-evoked release of endogenous 5-hydroxytryptamine from mouse frontal cortex.
The effect of baclofen, the GABAB-agent, on the potassium-evoked release of endogenous 5-hydroxytryptamine (5-HT) from slices of mouse frontal cortex has been investigated. The release of endogenous 5-HT evoked by addition of K+ (35 mM) was inhibited by (+/-)-baclofen in a dose-dependent manner with an IC50 of 0.1 microM. Inhibition of K+-evoked release of 5-HT was produced by (+/-)- and (-)-baclofen but not (+)-baclofen. This action of the (-)-enantiomer was not altered by the presence of the (+)-enantiomer. Addition of GABA (0.1-10 microM) also induced a dose-dependent inhibition of 5-HT release. This effect was neither enhanced by flurazepam (1 microM) nor antagonized by bicuculline (10 microM). The progabide metabolite, 4-[( (4-chlorophenyl) (5-fluoro-2-hydroxyphenyl)methylene]amino)butyric acid (SL75.102) (1 microM) inhibited the K+-evoked release of 5-HT by 61%. These data suggest that baclofen is a potent inhibitor of the K+-evoked release of endogenous 5-HT from the cortex and further indicate that the release of 5-HT may be controlled by a GABAB-receptor located presynaptically.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005479:Flurazepam / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D013237:Stereoisomerism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D000927:Anticonvulsants; D011963:Receptors, GABA-A; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; C017984:progabide acid; D001418:Baclofen; D005479:Flurazepam; D011188:Potassium; D002118:Calcium; D001640:Bicuculline