GABAergic modulation of acetylcholine release in cholinergic synaptosomes from Torpedo marmorata electric organ.
GABAA- and GABAB-receptor-specific agonists inhibit the depolarization-evoked release of acetylcholine in cholinergic synaptosomes from Torpedo electric organ. Over 60% of the release is inhibited by a 10(-4) M concentration of GABA itself. IC50s for muscimol and baclofen are 1.3 x 10(-4) and 2.2 x 10(-6) M, respectively. The effect of muscimol is totally blocked by the direct antagonist bicuculline methiodide, and also by the allosteric antagonists methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate, picrotoxinin and tert-butylbicyclo-orthobenzoate; the effect of baclofen is blocked by delta-aminovalerate. Furthermore, the inhibitory action of muscimol on acetylcholine release is substantially enhanced by flunitrazepam and pentobarbital. These results suggest the existence of typical GABAA and GABAB receptors in the presynaptic nerve terminals of the Torpedo electric organ regulating the liberation of acetylcholine and therefore the discharge of the electroplaques.
Ramírez
G
G
Centro de Biología Molecular, CSIC-UAM, Madrid, Spain.
Marsal
J
J
Barat
A
A
Solsona
C
C
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014101:Torpedo / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D000109:Acetylcholine; D011188:Potassium; D001640:Bicuculline