In vivo evidence that GABA(B) receptors are negatively coupled to adenylate cyclase in rat striatum.
The characteristics of the cerebral GABA(B) receptor/cyclic AMP (cAMP)-generating system were investigated using the in vivo microdialysis technique in freely moving rats. Addition of forskolin, an activator of adenylate cyclase, to perfusate for 20 min resulted in a dose-dependent increase of cAMP efflux from the striatum. Pre- and coinfusions of baclofen for 80 min had no effect on the basal efflux of cAMP from the striatum but induced a significant decrease of forskolin (10 microM)-stimulated cAMP efflux from the striatum in a dose-dependent manner. SKF 97541 (100 microM), a GABA(B) receptor agonist, and GABA (50 microM) also decreased forskolin-induced cAMP efflux from the striatum. Coinfusion of CGP 54626A (100 microM), a GABA(B) receptor antagonist, counteracted the effect of baclofen on the forskolin-stimulated cAMP efflux. In contrast, the isoproterenol (5 mM)-induced increase of cAMP efflux from the striatum was significantly enhanced by pre- and coinfusions with baclofen. These results suggest that this test system using in vivo microdialysis may be useful for examining the effect of drugs on the GABA(B) receptor-linked cAMP-generating system in vivo.
Hashimoto
T
T
Department of Pharmacology, Kyoto Prefectural University of Medicine, Kamikyo-ku, Japan.
Kuriyama
K
K
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000737:chemistry* / Q000201:enzymology; D000242:Cyclic AMP / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D007545:Isoproterenol / Q000494:pharmacology; D008124:Locomotion / Q000502:physiology; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D000318:Adrenergic beta-Agonists; D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; C068457:3-aminopropyl(methyl)phosphinic acid; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D001418:Baclofen; D007545:Isoproterenol