Forskolin attenuates the evoked release of [3H]GABA from striatal neurons in primary culture.
The actions of the diterpene forskolin, and cyclic AMP analogues, on the evoked release of [3H]GABA (gamma-aminobutyric acid) was examined in intact striatal neurons in primary culture, generated from the fetal mouse brain. Exposure of striatal neurons to forskolin (100 microM) resulted in a 40-55% attenuation of [3H]GABA release evoked by either KCl (30 mM) or veratrine (2 micrograms/ml), while baseline levels of release were unaffected. The dose-dependence for forskolin attenuation of KCl-evoked release of [3H]GABA was virtually identical to the dose-dependent elevation of cyclic AMP levels by forskolin in striatal neurons. Exposure of striatal neurons to membrane-permeable analogues of cyclic AMP, such as p-chlorophenylthio cyclic AMP (0.5 mM) and dibutyryl cyclic AMP (1 mM), resulted in a 25 and 26% attenuation of [3H]GABA release, respectively; dibutyryl cyclic GMP (1 mM) was without effect. The similarity between the actions of forskolin and the cyclic AMP analogues suggests that, in striatal neurons in primary culture, the elevation of cyclic AMP levels results in the attenuation of the evoked release of [3H]GABA. The greater effectiveness of forskolin, compared to the cyclic AMP analogues, may be related to the recently reported, additional direct actions of forskolin on neuronal membrane ion channels.
Weiss
S
S
Department of Psychiatry, University of Vermont College of Medicine, Burlington 05405.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D013873:Thionucleotides / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D013873:Thionucleotides; D005576:Colforsin; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D005680:gamma-Aminobutyric Acid; D003994:Bucladesine; D000242:Cyclic AMP