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

• Published in: European journal of pharmacology Vol. 478; no. 2; pp. 111 - 119
• Main Authors: Nyitrai, Gabriella, Kékesi, Katalin A, Emri, Zsuzsa, Szárics, Éva, Juhász, Gábor, Kardos, Julianna
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 2003
• Subjects: Brain; GABA (γ-aminobutyric acid); GABA B receptors; Glutamate; Hippocampus; rat; Somatostatin; Brain; GABA (γ-aminobutyric acid); Somatostatin; GABA B receptors; Glutamate; Hippocampus
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2003.08.006

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 μM. Simultaneous measurement of [ 14C]Glu and [ 3H]γ-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.