GABAB Receptor Signaling Pathways

  • S. J. Enna
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 150)


The GABAB receptor was first identified and characterized on the basis of its sensitivity to baclofen and insensitivity to bicuculline, benzodiazepines, and other agents known to interact with the GABAA site (Bowery et al. 1980). Earlier and subsequent electrophysiological studies with baclofen revealed that it causes a neuronal hyperpolarization and an increase in membrane conductance (Curtis et al. 1974; Newberry and Nicoll 1985). Unlike the GABAA receptor, which is a C1 ionophore, the electrophysiological responses to baclofen are due to changes in K+ and Ca++ conductances (Newberry and Nicoll 1985). Moreover, GABAB receptor activation inhibits the evoked release of a number of transmitters from brain tissue, including glutamate, serotonin, dopamine and GABA itself (Bowery et al. 1980; Gray and Green 1987; Huston et al. 1990; Pende et al. 1993). Taken together, these data provided compelling evidence that the GABAA and GABAB receptors represent pharmacologically, physiologically and molecularly distinct entities. The subsequent cloning of these sites provided unequivocal confirmation of this hypothesis (Barnard 1995; Mohler 1995; Kaupmann et al. 1997).


Adenylyl Cyclase GABAB Receptor cAMP Production cAMP Formation GABAB Receptor Agonist 
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