The GABA Receptors

Abstract

Summaryγ-Aminobutyric acid (GABA), an amino acid neurotransmitter, is widely distributed throughout the neuraxis. Two pharmacologically and molecularly distinct GABA receptors have been identified, GABA A and GABA B . GABA A receptors are pentameric ligand-gated chloride-ion channels, whereas GABA B receptors are heterodimeric G protein-coupled sites. Although GABA A receptor subtypes can display pharmacological differences, the two molecularly distinct GABA B receptors have similar substrate specificities, limiting the ability to selectively manipulate this site. Gene deletion and point mutation studies have revealed the importance of GABA receptors in neural development and function, with subtle modifications in subunit amino acid composition having profound effects on behavioral phenotype and responses to drugs. The characterization of GABA A receptors has contributed substantially to the knowledge about allosteric regulation of ligand-gated ion channels. Such information is invaluable in defining precisely the mechanisms of action of numerous drugs, such as the benzodiazepines, and toxic agents. Research on GABA B receptors has proven the existence of dimeric metabotropic receptors and has provided the chemical tools necessary for defining such systems. The characterization of the pentameric GABA A and dimeric GABA B receptors has been crucial for understanding the neurobiological basis of some nervous system disorders. Given the importance of GABA in central nervous system function, further work on its receptors is likely to yield novel therapeutics for treating a host of neurological and psychiatric conditions.

A facilitatory effect of bicuculline on the enteric neurones in the guinea‐pig isolated colon

“…Measurement of the functional effects of GABA receptor blockade by competitive antagonists is considered to be a reliable pharmacological tool to assess the role of GABAergic neurotransmission in the CNS (Enna, 1983). Bicuculline, although not completely devoid of non-specific effects, is still commonly employed as the reference drug for competitive antagonism on GABA receptors (Curtis et al, 1971; Figure 5 Effect of bicuculline on the guinea-pig colon longitudinal muscle responses to nerve stimulation.…”

Benzodiazepine/gamma-aminobutyric acid receptor deficit in the midbrain of the seizure-susceptible gerbil.

“…Treatments that interfere with GABA function cause seizures, whereas enhancement of GABA function can protect against seizures (1). The most common type of GABA-mediated inhibitory transmission involves regulation of postsynaptic membrane chloride ion channels by receptor sites defined by sensitivity to the agonist muscimol and the antagonist bicuculline (2). These GABA receptors contain modulatory sites for the important anticonvulsant drugs, the benzodiazepines and the barbiturates, consistent with evidence that these drugs enhance GABA postsynaptic actions and that this is involved in their therapeutic effects (3).…”

Acid–base physiology, neurobiology and behaviour in relation to CO2-induced ocean acidification

“…However, no other study found any effect of gabazine on behaviour (Chivers et al, 2014;Lai et al, 2015;Lopes et al, 2016;Munday et al, 2016;Nilsson et al, 2012;Watson et al, 2014) or visual processing (Chung et al, 2014) in control fish. This is an interesting point because gabazine should also affect normal inhibitory GABA regulation, inducing neuronal excitation; in fact, one of the features precluding the use of gabazine as a therapeutic agent in humans is the risk of convulsions resulting from inappropriate neuronal excitation (Enna and Bowery, 1997). A similar effect was seen in intact zebrafish (Danio rerio) brains, where gabazine increased the spontaneous firing rate of olfactory neurons, altered the dynamics of odour-induced firing, blocked fast oscillatory synchronization of local neurons and induced epileptiform activity (Tabor et al, 2008).…”