ABSTRACT
The neurotransmitter -amino-butyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system. Diverse actions of GABA neurotransmission are mediated by three types of receptors. On the basis of pharmacological, physiological and molecular criteria they can be classified into two distinct groups: GABA-gated chloride channels (GABAA/C) and metabotropic G-protein coupled receptors (GABAB; for reviews see Bowery, 1993, Borman and Feigenspan, 1995; Kerr and Ong, 1995; Smith and Olson, 1995). It was only in 1981 that Norman Bowery and his colleagues were able to define the GABAB receptor pharmacologically by the selective agonist L-baclofen and its insensitivity to bicuculline, a GABAA receptor antagonist (Hill and Bowery, 1981). Whereas binding of GABA to GABAA/C leads to fast synaptic inhibition, the effect of activating GABAB receptors results in activating multistep pathways via guanine-nucleotide-binding proteins. Hence slow and long-lasting inhibitory signals are produced. To date, the physiological role of GABAB receptors is only poorly understood. Neurophysiological and pharmacological studies suggest, however, that malfunctioning of the receptor could be involved in the development of chronic pain, spasticity and epileptogenesis of absence seizures.
