gamma-Aminobutyric acid-B receptors inhibit glutamate release from cerebellar granule cells: consequences of inhibiting cyclic AMP formation and calcium influx.
In cerebellar granule cells, baclofen acted with micromolar concentrations at proposed gamma-aminobutyric acid-B receptors to inhibit the formation of cyclic AMP and depolarization-induced release of glutamate. Nanomolar concentrations of baclofen inhibited depolarization-induced influx of calcium. All three responses to baclofen were attenuated after pertussis toxin pretreatment of cell cultures. The inhibition of calcium influx and glutamate release were reversed by the cyclic AMP analog, 8-(4-chlorphenylthio)-cyclic AMP. The release of glutamate was dependent on the influx of extracellular calcium, which enters the cell through dihydropyridine-sensitive voltage-dependent calcium channels. Because the decrease in calcium influx by baclofen and nifedipine were additive, the baclofen-mediated decrease in calcium influx may not involve a dihydropyridine-sensitive calcium channel. These results show similarities between the baclofen-mediated inhibition of cyclic AMP formation and glutamate release, suggesting a relationship between these two events. The baclofen-mediated inhibition of calcium influx may not be related to baclofen's inhibition of glutamate release.
Travagli
R A
RA
Fidia Georgetown Institute for the Neurosciences, Georgetown University School of Medicine, Washington, DC.
Ulivi
M
M
Wojcik
W J
WJ
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001418:Baclofen / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology; D004789:Enzyme Activation; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D007424:Intracellular Fluid / Q000378:metabolism; D037342:Pertussis Toxin; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D015220:Calcium Channels; D004095:Dihydropyridines; D005971:Glutamates; D011963:Receptors, GABA-A; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D018698:Glutamic Acid; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D011189:Potassium Chloride; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D001418:Baclofen; D002118:Calcium