U-46619, a Selective Thromboxane A₂ Mimetic, Inhibits the Release of Endogenous Noradrenaline From the Rat Hippocampus In Vitro

抄録

Possible roles of thromboxane A₂(TXA₂)in the release mechanism of hippocampal noradrenaline(NA)were examined in vitro.Slices or crude synaptosomes prepared from the rat hippocampus were superfused with modified Krebs-Ringer solution.Application of 20mM KCl for 5min increase the release of NA from the slices, and this release was consistently reproduced.Application of U-46619(9, 11-dideoxy-9α, 11α-methanoepoxy prostaglandin F_2α), a specific TXA₂ mimetic, just before the second KCl(20mM)stimulation decreased the KCl-evoked NA release in a concentration-dependent manner(10-100μM).This U-46619(50μM)-induced inhibition of NA release was abolished by 10μM SQ29548, a specific TXA₂ receptor antagonist.In experiments with hippocampal crude synaptosomes, however, KCl(20 and 40mM)-evoked release of NA was not attenuated by U-46619(100μM).Furthermore, the inhibitory effect of U-46619(50μM)in the sliced preparations was not modified by 100μM(−)-bicuculline, a GABA_A-receptor antagonist.The present results indicate that U-46619 inhibits the release of NA from the rat hippocampus by activation of TXA₂ receptors.Activation of TXA₂ receptors probably excites an unidentified but not GABAergic neuron system, thereby inhibiting the NA release from the rat hippocampus.