GABAB receptor-mediated effects in synaptosomes of lethargic (lh/lh) mice.
Previously, we have shown a significant increase in number of GABAB receptor binding sites in neocortex and thalamus of lethargic (lh/lh) mice, a mutant strain exhibiting absence seizures. This study was performed to test our hypothesis that presynaptic GABAB receptors would inhibit [3H]GABA release to a greater degree in lh/lh mice compared with their nonepileptic littermates (designated +/+). Synaptosomes isolated from neocortex and thalamus of age-matched male lh/lh and +/+ mice were similar in uptake of [3H]GABA. In the neocortical preparation, baclofen dose-dependently inhibited [3H]GABA release evoked by 12 mM KCl, an effect mediated by GABAB receptors. The maximal inhibition (Imax) value was significantly greater (80%) in lh/lh than +/+ mice, whereas the IC50 (3 microM) was unchanged. In the thalamic preparation, the effect of baclofen (50 microM) was 58% less robust in lh/lh mice. Other effects mediated by GABAB receptors (inhibitions in Ca2+ uptake and cyclic AMP formation) were also significantly reduced in thalamic synaptosomes from lh/lh mice. These data suggest a greater presynaptic GABAB receptor-mediated effect in neocortex and a reduced effect in thalamic nuclei of lh/lh mice. It is possible that selective effects of presynaptic GABAB receptors or GABA release in neocortex and thalamic nuclei of lh/lh mice may contribute to mechanisms underlying absence seizures.
Lin
F H
FH
Department of Medicine (Neurology), Duke University, Durham, North Carolina, USA.
Wang
Y
Y
Lin
S
S
Cao
Z
Z
Hosford
D A
DA
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism; D004832:Epilepsy, Absence / Q000235:genetics / Q000503:physiopathology*; D006824:Hybridization, Genetic; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011189:Potassium Chloride / Q000494:pharmacology; D018080:Receptors, GABA-B / Q000502:physiology*; D013574:Synaptosomes / Q000502:physiology*; D013788:Thalamus / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018080:Receptors, GABA-B; D005576:Colforsin; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D000242:Cyclic AMP; D002118:Calcium