Modulation of adenylyl cyclase activity by baclofen in the developing rat brain: difference between cortex, thalamus and hippocampus.
Ontogenetic changes in the levels of GABA(B) receptors and their ability to modulate adenylyl cyclase (AC) activity were analyzed in rat cortex, thalamus and hippocampus. The relative numbers of GABA(B) receptors (measured as saturable, high-affinity [(3)H](-)baclofen binding sites) in cortex and thalamus were high already at postnatal day 1 (PD 1) and they reached a maximum at PD 25 and PD 12, respectively. There were no detectable high-affinity [(3)H](-)baclofen binding sites in hippocampus between birth and PD 12 and low-affinity [(3)H](-)baclofen binding attained at PD 12 did not change in adulthood (PD 90). Whereas GTP-stimulated AC activity in cortex and thalamus was depressed by baclofen, it was enhanced in hippocampus. These data indicate that the inhibitory effect of baclofen on AC in cortex and thalamus is primarily mediated through the alpha subunits of G(i)/G(o) proteins. The stimulatory effect of baclofen in hippocampus may be explained by engagement of Gbetagamma subunits.
Hejnová
Lucie
L
Department of Biochemistry of Membrane Receptors, Institute of Physiology, Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic.
Ihnatovych
Ivanna
I
Novotny
Jiri
J
Kubová
Hana
H
Mares
Pavel
P
Svoboda
Petr
P
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001418:Baclofen / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism; D013788:Thalamus / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development
D018080:Receptors, GABA-B; D000262:Adenylyl Cyclases; D001418:Baclofen