U-46619, a selective thromboxane A(2) mimetic, inhibits the release of endogenous noradrenaline from the rat hippocampus in vitro

Possible roles of thromboxane A(2) (TXA(2)) in the release mechanism of hip pocampal noradrenaline (NA) were examined in vitro. Slices or crude synapto somes prepared from the rat hippocampus were superfused with modified Krebs -Ringer solution. Application of 20 mM KCl for 5 min increased the release of NA from the slices, and this release was consistently reproduced. Applic ation of U-46619 (9,11-dideoxy-9 alpha,11 alpha-methanoepoxy prostaglandin F-2 alpha a specific TXA(2) mimetic, just before the second KCI (20 mM) sti mulation decreased the KCl-evoked NA release in a concentration-dependent m anner (10-100 mu M), This U-46619 (50 mu M)-induced inhibition of NA releas e was abolished by 10 mu M SQ29548, a specific TXA(2) receptor antagonist. In experiments with hippocampal crude synaptosomes, however, KCl (20 and 40 mM)-evoked release of NA was not attenuated by U-46619 (100 mu M). Further more, the inhibitory effect of U-46619 (50 mu M) in the sliced preparations was not modified by 100 mu M (-)-bicuculline, a GABA(A)-receptor antagonis t. The present results indicate that U-46619 inhibits the release of NA fro m the rat hippocampus by activation of TXA(2) receptors. Activation of TXA( 2) receptors probably excites an unidentified but not GABAergic neuron syst em, thereby inhibiting the NA release from the rat hippocampus.