Increased baclofen-stimulated G protein coupling and deactivation in rat brain cortex during development

Brain Res Dev Brain Res. 2004 Jul 19;151(1-2):67-73. doi: 10.1016/j.devbrainres.2004.03.014.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Baclofen / pharmacology*
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / growth & development
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • GABA Agonists / pharmacology
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Proteins / physiology*
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Male
  • Organophosphorus Compounds / pharmacokinetics
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Proteins / pharmacology
  • RGS Proteins / pharmacology
  • Radioligand Assay / methods
  • Rats
  • Tritium / pharmacokinetics

Substances

  • GABA Agonists
  • Organophosphorus Compounds
  • Proteins
  • RGS Proteins
  • RGS16 protein
  • Rgs1 protein, rat
  • Tritium
  • CGP 54626
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • Baclofen