GABA B receptors

Abstract

cAMP= : cyclic adenosine monophosphate; ER= : endoplasmic reticulum; GABA= : γ-aminobutyric acid; GAT= : γ-aminobutyric acid transporters; PKA= : protein kinase A; RT= : reticular thalamic; SCLC= : small-cell lung cancer; TC= : thalamocortical. γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS and has a key role in modulating neuronal activity. GABA mediates its action via 2 classes of receptors, ionotropic GABAA and GABAC and metabotropic GABAB receptors. Unlike GABAA and C receptors, which form chloride channels and are involved in fast synaptic inhibition, GABAB receptors are guanine nucleotide-binding (G) protein-coupled receptors that modulate calcium (Ca2+) and potassium (K+) channels and elicit both presynaptic and slow postsynaptic inhibition. GABAB receptors are broadly expressed in the nervous system, modulating synaptic excitability and plasticity in the cerebral cortex, generating rhythmic activity in cortical and thalamic circuits, relaying primary afferent input to the spinal cord and brainstem, and affecting the activity of dopaminergic and other monoaminergic neurons. These receptors have been implicated in a wide variety of neurologic and psychiatric disorders, including absence seizures, γ-hydroxybutyrate toxicity, and, more recently, autoimmune limbic encephalitis. Baclofen is the only clinically available GABAB receptor agonist and is utilized for treatment of spasticity, dystonia, and some types of neuropathic pain. GABAB receptors may also provide a target for management of drug addiction, anxiety, and visceral pain. The structure, functions, and clinical implications of GABAB receptors have been extensively reviewed1,–,7 ### Subunit composition. GABAB receptors, like other G protein–coupled receptors, have a central core domain, constituted of 7 transmembrane helices, that is responsible for G-protein coupling. These receptors are members of class C G protein–coupled receptors, which also includes the metabotropic glutamate receptors, the calcium sensing receptor, and some taste receptors. The GABAB receptor, like other members of this class, is an obligatory heterodimer in vivo and is formed by 2 subunits, GABAB1 and GABAB23,8 (figure 1). The GABAB1 …