GABA_B Receptor‐Mediated Enhancement of Vasoactive Intestinal Peptide‐Stimulated Cyclic AMP Production in Slices of Rat Cerebral Cortex

<jats:title>Abstract:</jats:title><jats:p>Basal and vasoactive intestinal peptide (VIP)‐stimulated accumulations of cyclic AMP were measured in slices of rat cerebral cortex. Neither γ‐aminobutyric acid (GABA) nor the selective GABA<jats:sub>B</jats:sub> receptor agonist (–)‐baclofen stimulated basal cyclic AMP accumulation, whereas VIP caused a large dose‐dependent increase in cyclic AMP levels. However, in the presence of 100 μ<jats:italic>M</jats:italic> (–)‐baclofen, the effects of VIP on cyclic AMP accumulation were significantly enhanced, with the responses to 1 μ<jats:italic>M</jats:italic> and 10 μ<jats:italic>M</jats:italic> VIP being approximately doubled. The enhancing effects of (–)‐baclofen was dose related (1–1,000 μ<jats:italic>M</jats:italic>), but an enhancing effect was not observed with 100 μ<jats:italic>M</jats:italic> (+)‐baclofen. In the presence of the GABA uptake inhibitor nipecotic acid (1 m<jats:italic>M</jats:italic>), GABA caused a similar dose‐related enhancement of the VIP response. The ability of either GABA or (–)‐baclofen to augment VIP‐stimulated production of cyclic AMP was not mimicked by the GABA<jats:sub>A</jats:sub> agonists isoguvacine and 4,5,6,7‐ tetrahydroisoxazolo[5,4‐<jats:italic>c</jats:italic>]pyridin‐3‐ol (THIP) and was not antagonized by the GABA<jats:sub>A</jats:sub> antagonist bicuculline. The putative GABA<jats:sub>B</jats:sub> antagonist 5‐aminovaleric acid (1 m<jats:italic>M</jats:italic>) significantly reduced the effect of (–)‐baclofen. The ability of (–)‐baclofen to enhance VIP‐stimulated accumulation of cyclic AMP was observed in slices of rat cerebral cortex, hippocampus, and hypothalamus. These results indicate that GABA and (–)‐baclofen can enhance VIP‐stimulated accumulation of cyclic AMP in rat brain slices via an interaction with specific GABA<jats:sub>B</jats:sub> receptors.</jats:p>