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Eur J Pharmacol. 2003 Oct 8;478(2-3):111-9.

GABA(B) receptor antagonist CGP-36742 enhances somatostatin release in the rat hippocampus in vivo and in vitro.

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1
Department of Neurochemistry, Chemical Research Center, Hungarian Academy of Sciences, H-1025 Budapest, Pusztaszeri út 59-67, Hungary. nyitraig@chemres.hu

Abstract

Here, we show the modulation of somatostatin functions in the hippocampus by the orally active 'cognition enhancer' GABA(B) receptor antagonist, (3-aminopropyl)n-butylphosphinic acid (CGP-36742), both in vivo and in vitro. Using high-pressure liquid chromatography-coupled electrospray mass spectrometry, we measured a two-fold increase in the extracellular level of somatostatin to CGP-36742 application in the hippocampus of anaesthetised rats. The basal release of [125I]somatostatin in the synaptosomal fraction was increased by CGP-36742 in concentrations lower than 1 muM. Simultaneous measurement of [14C]Glu and [3H]gamma-aminobutyric-acid ([3H]GABA) showed that CGP-36742 increased their basal release. However, prior [125I]somatostatin application suppressed the increase in the basal release of [14C]Glu and induced a net decrease in the basal release of [3H]GABA. Somatostatin application had a similar effect. In slices, CGP-36742 increased the postsynaptic effect of somatostatin on CA1 pyramidal cells. These results suggest a pre- and postsynaptic functional 'cross-talk' between coexisting GABA(B) and somatostatin receptors in the rat hippocampus.

PMID:
14575795
[Indexed for MEDLINE]
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