Studies on the mechanism of modulation of [(3)H]noradrenaline release from rat hippocampal synaptosomes by GABA and benzodiazepine receptors.
Release of [(3)H]noradrenaline from rat hippocampal synaptosomes was triggered by pulses of 25 mM K(+), 5 ?M veratridine or superfusion with the Ca(2+) ionophore A23187. GABA with bicuculline or chlordiazepoxide depressed the release of [(3)H]noradrenaline evoked by depolarisation but not by the Ca(2+) ionophore. 8 Br-cAMP with [Ca(2+)](0) 0.3 mM had no effect on spontaneous or K(+)-evoked release of [(3)H]noradrenaline and completely blocked the effect of chlordiazepoxide and GABA with bicuculline. With [Ca(2+)](0) 1 mM 8 Br-cAMP enhanced spontaneous and K(+)-evoked release of [(3)H]noradrenaline, and reversed the depression caused by GABA with bicuculline. GABA alone evoked Ca(2+)-dependent release of [(3)H]noradrenaline which was sensitive to [Cl(?)](0). The results suggest that the GABA(A)-receptor mediated release of [(3)H]noradrenaline is due to depolarisation resulting from increased Cl(?) conductance whereas the depression of depolarisation-dependent release of [(3)H]noradrenaline by GABA(B) or benzodiazepine receptors is mediated by a cAMP-dependent decrease in the voltage-dependent Ca(2+) conductance.
Fung
S C
SC
University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, U.K.
Fillenz
M
M