Abstract
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 language | English (US) |
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Pages (from-to) | 439-443 |
Number of pages | 5 |
Journal | Brain Research Bulletin |
Volume | 21 |
Issue number | 3 |
DOIs | |
State | Published - Sep 1988 |
Externally published | Yes |
Keywords
- 3-Aminopropylphosphonic acid
- Baclofen
- Cyclic AMP
- GABA receptors
ASJC Scopus subject areas
- Neuroscience(all)