GABAB Receptors: Molecular Organization, Function, and Alternative Drug Development by Targeting Protein-Protein Interactions

GABAB receptors couple via Gi/o proteins to multiple effector proteins to mediate prolonged inhibition in the nervous system. They are important elements in maintaining the excitation/inhibition balance by controlling neuronal excitation. GABAB receptors are expressed in virtually all neurons and are involved in the regulation of most brain functions. In neurological diseases associated with a disturbed excitation/inhibition balance, GABAB receptors are often de-regulated and represent promising drug targets for the development of novel therapeutic interventions. In this chapter, we briefly review the basic functions and the structural organization of the receptors. Then, we describe pathways that de-regulate GABAB receptors in neuropathic pain, cerebral ischemia, and psychostimulant-induced addiction and discuss efforts for alternative drug discovery by targeting disease-relevant protein-protein interactions.