Jpn. J. Pharmacol. 82 (3), 226-231 (2000)

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

Makoto Nishihara1,2, Kunihiko Yokotani2,*, Shimpei Inoue1 and Yoshitsugu Osumi2

1Department╩of Neuropsychiatry and 2Department of Pharmacology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan
*╩To whom correspondence should be addressed.

Abstract: 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 20╩mM KCl for 5╩min increased the release of NA from the slices, and this release was consistently reproduced. Application of U-46619 (9,11-dideoxy-9a,11a-methanoepoxy prostaglandin╩F2a), a specific TXA2 mimetic, just before the second KCl (20╩mM) stimulation decreased the KCl-evoked NA release in a concentration-dependent manner (10-100╩mM). This U-46619 (50╩mM)-induced inhibition of NA release was abolished by 10╩mM SQ29548, a specific TXA2 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╩mM). Furthermore, the inhibitory effect of U-46619 (50╩mM) in the sliced preparations was not modified by 100╩mM (-)-bicuculline, a GABAA-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.

Keywords: Thromboxane╩A2 (TXA2), Noradrenaline release, Hippocampus, U-46619, TXA2 mimetic

Copyrightę The Japanese Pharmacological Society 2000

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