Makoto Nishihara1,2, Kunihiko Yokotani2,*, Shimpei
Inoue1 and Yoshitsugu Osumi2
1Departmentﾊof Neuropsychiatry and 2Department
of Pharmacology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan
*ﾊTo whom correspondence should be addressed.
Abstract: Possible roles of thromboxaneﾊ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ﾊmM
KCl for 5ﾊ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ﾊF2a), a specific TXA2
mimetic, just before the second KCl (20ﾊmM) stimulation decreased the KCl-evoked
NA release in a concentration-dependent manner (10-100ﾊmM).
This U-46619 (50ﾊmM)-induced inhibition of NA
release was abolished by 10ﾊmM SQ29548, a specific
TXA2 receptor antagonist. In experiments with hippocampal crude
synaptosomes, however, KCl (20 and 40ﾊmM)-evoked release of NA was not attenuated
by U-46619 (100ﾊmM). Furthermore, the inhibitory
effect of U-46619 (50ﾊmM) in the sliced preparations
was not modified by 100ﾊ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ﾊA2 (TXA2), Noradrenaline
release, Hippocampus, U-46619, TXA2 mimetic