title: Increased baclofen-stimulated G protein coupling and deactivation in rat brain cortex during development.
abstract: The number and affinity of GABA(B) receptors (assayed by the specific antagonist [(3)H]CGP54626A) was unchanged when compared in carefully washed cerebrocortical membranes from young (12-day-old) and adult (90-day-old) rats. In contrast, high-affinity GTPase activity, both basal and baclofen-stimulated was significantly higher (by 45% and 56%, respectively) in adult than in young rats. Similar results were obtained by concomitant determination of agonist (baclofen)-stimulated GTP gamma S binding. Under standard conditions, baclofen-stimulated GTPase activity was further considerably enhanced by exogenously added regulator of G protein function, RGS1, but not by RGS16. RGS16 was able to affect agonist-stimulated GTPase activity only in the presence of markedly increase substrate (GTP) concentrations. RGS1 alone slightly increased GTPase activity in adult rats, but neither RGS1 nor RGS16 influenced GTPase activity in membrane preparations isolated from young animals. These findings indicate increasing functional activity of trimeric G protein(s) involved in GABAergic transmission in the developing rat brain cortex and suggest a high potential of RGS1 in regulation of high-affinity GTPase activity.
authors.affiliation: Department of Membrane Receptors, Institute of Physiology, Academy of Sciences, Videnska 1083, 142 20, Prague 4, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Stöhr
authors.forename: Lenka
authors.initials: L
authors.lastname: Bourova
authors.forename: Lucie
authors.initials: L
authors.lastname: Hejnova
authors.forename: Ivanna
authors.initials: I
authors.lastname: Ihnatovych
authors.forename: Jiri
authors.initials: J
authors.lastname: Novotny
authors.forename: Petr
authors.initials: P
authors.lastname: Svoboda
mesh_terms: D000375:Aging / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001418:Baclofen / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018755:GABA Agonists / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D008297:Male; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011506:Proteins / Q000494:pharmacology; D020710:RGS Proteins / Q000494:pharmacology; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D018755:GABA Agonists; D009943:Organophosphorus Compounds; D011506:Proteins; D020710:RGS Proteins; C107413:RGS16 protein; C489853:Rgs1 protein, rat; D014316:Tritium; C107353:CGP 54626; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D001418:Baclofen