GABAB receptor-mediated enhancement of vasoactive intestinal peptide-stimulated cyclic AMP production in slices of rat cerebral cortex.
Basal and vasoactive intestinal peptide (VIP)-stimulated accumulations of cyclic AMP were measured in slices of rat cerebral cortex. Neither gamma-aminobutyric acid (GABA) nor the selective GABAB 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 microM (-)-baclofen, the effects of VIP on cyclic AMP accumulation were significantly enhanced, with the responses to 1 microM and 10 microM VIP being approximately doubled. The enhancing effects of (-)-baclofen was dose related (1-1,000 microM), but an enhancing effect was not observed with 100 microM (+)-baclofen. In the presence of the GABA uptake inhibitor nipecotic acid (1 mM), 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 GABAA, agonists isoguvacine and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) and was not antagonized by the GABAA antagonist bicuculline. The putative GABAB antagonist 5-aminovaleric acid (1 mM) 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 GABAB receptors.
D000596:Amino Acids / Q000494:pharmacology; D021542:Amino Acids, Neutral; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000596:Amino Acids; D021542:Amino Acids, Neutral; D007555:Isoxazoles; D011963:Receptors, GABA-A; D014660:Vasoactive Intestinal Peptide; D005680:gamma-Aminobutyric Acid; C013809:5-aminovaleric acid; C036615:bicuculline methobromide; D000242:Cyclic AMP; D001418:Baclofen; C015542:gaboxadol; D001640:Bicuculline