GABAB receptor-mediated inhibition of forskolin-stimulated cyclic AMP accumulation in rat spinal cord.
GABA (30-1000 microM) and the GABAB agonist, (-)baclofen (10-100 microM), but not (+)baclofen, inhibited forskolin-induced cAMP formation in rat spinal cord slices. In contrast, GABA and (-)baclofen failed to enhance the stimulation of cAMP induced by noradrenaline in the same tissue, even though they both increased the response to noradrenaline in cerebral cortex slices. Neonatal capsaicin treatment, which reduces the density of GABAB binding sites in the cord, did not modify the effect of GABA or (-)baclofen on the forskolin-induced elevation of cAMP. (-)Baclofen and GABA inhibition of forskolin effects were insensitive to the GABAB antagonists CGP 35348 and CGP 36742 in the spinal cord. Since CGP 35348 antagonizes baclofen-induced antinociception, it seems unlikely that this effect stems from any change in cAMP within the spinal cord.
Malcangio
M
M
Department of Pharmacology, School of Pharmacy, London, UK.
Bowery
N G
NG
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001418:Baclofen / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis*; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000700:Analgesics; D058787:GABA-A Receptor Antagonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; C079148:(3-aminopropyl)(n-butyl)phosphinic acid; D005576:Colforsin; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; D000242:Cyclic AMP; D001418:Baclofen; D002211:Capsaicin; D009638:Norepinephrine