Evidence for pharmacologically distinct subsets of GABAB receptors

Roberta W. Scherer, John W. Ferkany, S. J. Enna

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Activation of GABAB receptors augments neurotransmitter-stimulated cyclic AMP accumulation while inhibiting forskolin-mediated second messenger production. Previous studies have revealed that GABAB receptors are associated with a pertussis toxin sensitive G protein, such as Gi. While such a linkage is consistent with the finding that GABAB receptor activation inhibits forskolin-mediated second messenger accumulation, it fails to explain how GABAB agonists are capable of augmenting receptor-mediated cyclic AMP production. The present experiments were undertaken to explore the possible existence of pharmacologically distinct GABAB receptors in an attempt to explain this apparent discrepancy. For the study, a variety of agents were examined for their ability to inhibit GABAB binding to brain membranes and to modify isoproterenol- or forskolin-stimulated second messenger production in rat brain slices. Of the compounds studied, only 3-aminopropylphosphonic acid and 4-aminobutylphosphonic acid were found to inhibit GABAB binding. However, 4-aminobutylphosphonic acid failed to influence either isoproterenol- or forskolin-stimulated cyclic AMP production. On the other hand, while 3-aminopropylphosphonic acid also failed to affect isoproterenol-stimulated second messenger accumulation, it inhibited the forskolin-mediated response. Given this finding, and the fact that some of the agents tested are known to influence GABAB receptor function in other systems, the results indicate a multiplicity of pharmacologically distinct GABAB receptor recognition sites. This discovery paves the way for the development of more selective GABAB receptor agonists and antagonists possessing different therapeutic potentials.

Original languageEnglish (US)
Pages (from-to)439-443
Number of pages5
JournalBrain Research Bulletin
Issue number3
StatePublished - Sep 1988
Externally publishedYes


  • 3-Aminopropylphosphonic acid
  • Baclofen
  • Cyclic AMP
  • GABA receptors

ASJC Scopus subject areas

  • General Neuroscience


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