GABA(B) receptor activation protects GABA(A) receptor from cyclic AMP-dependent down-regulation in rat cerebellar granule cells.
Interaction between GABAA and GABA(B) receptors was studied in rat cerebellar granule cells in culture, by the whole-cell patch-clamp approach. Our data show that the GABA(B) agonist (-)baclofen is not able, per se, to significantly change the muscimol-activated chloride current. However, (-)baclofen dose-dependently prevents the reduction of GABA(A) receptor function by forskolin, an activator of adenylate cyclase. The effect of baclofen is mediated by a pertussis toxin-sensitive G protein. In fact, in cells treated with pertussis toxin, baclofen and forskolin, the toxin is able to block baclofen action, allowing forskolin to act fully. The protective effect by GABA(B) receptor activation under these circumstances is most probably related to the prevention of cyclic AMP increases after forskolin treatment. In fact, in these neurons cyclic AMP and protein kinase A activation result in a down-regulation of GABA(A) receptor function. On the whole, the data indicate the presence of complex modulation of GABA(A) receptors by GABA(B) receptor types in cerebellum granule cells.
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INFM, Dipartimento di Fisica dell'Università di Genova, Italy.
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Robello
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D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002525:Cerebellar Cortex / Q000166:cytology* / Q000187:drug effects; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D018755:GABA Agonists / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000096:biosynthesis*; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D018118:Chloride Channels; D018755:GABA Agonists; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D009118:Muscimol; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases; D001418:Baclofen