GABAB Receptor Signaling Pathways

Enna, S.J.

doi:10.1007/978-3-642-56833-6_13

Cited by 8 publications

(5 citation statements)

References 65 publications

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“…Two pharmacologically and molecularly distinct GABA receptors have been identified, GABA A and GABA B . GABA B receptors are heterodimeric G protein-coupled sites, located both pre- and postsynaptically [ 3 , 4 ]. GABA B receptors are widely used in the treatment of neurologic and psychiatric disorders including absence seizures and gamma-hydroxybutyrate toxicity and more recently used for the treatment of autoimmune limbic encephalitis [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Effect ofGABABReceptor Antagonist (CGP35348) on Learning and Memory in Albino Mice

Gillani

Iqbal

Arfa

et al. 2014

The Scientific World Journal

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The present study was designed to demonstrate the potential effect of CGP 35348 (GABAB receptor antagonist) on the learning, memory formation, and neuromuscular coordination in albino mouse. Mice were intrapertoneally injected with 1 mg CGP 35348/mL of distilled water/Kg body weight, while the control animals were injected with equal volume of saline solution. A battery of neurological tests was applied following the intrapertoneal injections. Results of rota rod indicated that CGP 35348 had no effect on neuromuscular coordination in both male (P = 0.528) and female (P = 0.125) albino mice. CGP 35348 treated females demonstrated poor exploratory behavior during open filed for several parameters (time mobile (P = 0.04), time immobile (P = 0.04), rotations (P = 0.04), and anticlockwise rotations (P = 0.038)). The results for Morris water maze (MWM) retention phase indicated that CGP 35348 treated male mice took shorter latency to reach the hidden platform (P = 0.04) than control indicating improved memory. This observation was complemented by the swim strategies used by mice during training days in MWM as CGP 35348 treated males used more direct and focal approach to reach the platform as the training proceeded.

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Section: Introductionmentioning

confidence: 99%

Effect ofGABABReceptor Antagonist (CGP35348) on Learning and Memory in Albino Mice

Gillani

Iqbal

Arfa

et al. 2014

The Scientific World Journal

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“…The metabotropic GABA B receptor is a heterodimer composed of a GABA B receptor 1a (GBR1a) or GBR1b subunit and a GBR2 subunit (Bettler & Kaupmann, 2000; Bowery & Enna, 2000). Stimulated GABA B receptors couple to G i/o proteins and, typically, activate potassium channels and inhibit voltage‐dependent calcium channels (Gage, 1992; Bowery, 1993; Lüscher et al ., 1997; Isaacson, 1998; Bowery & Enna, 2000; Enna 2000). GABA B receptors regulate the function of neurons both in the somadendritic and in the axon terminal region.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the function of GABA_B receptors on inhibitory afferent neurons of Purkinje cells in the cerebellar cortex of the rat

Than

Szabó

2002

Eur J of Neuroscience

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Purkinje cells, the output neurons of the cerebellar cortex, receive inhibitory input from basket, stellate and neighbouring Purkinje cells. The aim of the present study was to clarify the role of GABAB receptors on neurons giving inhibitory input to Purkinje cells. In sagittal slices prepared from the cerebellar vermis of the rat, the GABAB receptor agonist baclofen lowered the frequency and amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) recorded in Purkinje cells. These effects were prevented by the GABAB receptor antagonist CGP 55845. Two mechanisms were involved in the depression of the inhibitory input to Purkinje cells. The first mechanism was suppression of the firing of basket, stellate and Purkinje cells. The second mechanism was presynaptic inhibition of GABA release from terminals of the afferent axons. This was indicated by the finding that baclofen decreased the amplitude of IPSCs occurring in Purkinje cells synchronously with action potentials recorded in basket cells. A further support for the presynaptic inhibition is the observation that baclofen decreased the amplitude of autoreceptor currents which are due to activation of GABAA autoreceptors at axon terminals of basket cells by synaptically released GABA. The presynaptic inhibition was partly due to direct inhibition of the vesicular release mechanism, because baclofen lowered the frequency of miniature IPSCs recorded in Purkinje cells in the presence of cadmium and in the presence of tetrodotoxin plus ionomycin. The results show that activation of GABAB receptors decreased GABAA receptor-mediated synaptic input to cerebellar Purkinje cells both by lowering the firing rate of the inhibitory input neurons and by inhibiting GABA release from their axon terminals with a presynaptic mechanism.

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“…Activation of GABA B receptors also reduces neuronal calcium conductance, an effect believed to be responsible for baclofen-induced inhibition of neurotransmitter release (43). In all cases it appears the GABA B receptor-mediated changes in ion channel activities are owing to liberation of G protein subunits which, in turn, directly influence channel function and the generation of second messengers (40,41). Persistent activation of GABA B receptors leads to desensitization through a GRK4-dependent process (see Chapter 10).…”

Section: Molecular Pharmacologymentioning

confidence: 98%

“…Subsequently it was discovered that baclofen and GABA regulate the stimulated release of various neurotransmitters through activation of a receptor that is pharmacologically distinct from the bicuculline-sensitive sites (39). These receptors, termed GABA B , are located both pre-and postsynaptically and, unlike the GABA A site, are coupled to G proteins (40,41). As the GABA B receptor is associated with G i and G o its stimulation reduces the activity of adenylyl cyclase or, through coincident signaling, enhances the production of cyclic AMP (40,41).…”

Section: Molecular Pharmacologymentioning

confidence: 98%

“…These receptors, termed GABA B , are located both pre-and postsynaptically and, unlike the GABA A site, are coupled to G proteins (40,41). As the GABA B receptor is associated with G i and G o its stimulation reduces the activity of adenylyl cyclase or, through coincident signaling, enhances the production of cyclic AMP (40,41). The predominant response to GABA B receptor activation is an increase in potassium conductance with a consequent hyperpolarization of the neuron (42).…”

Section: Molecular Pharmacologymentioning

confidence: 99%

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The GABA Receptors

Enna

The Receptors

Self Cite

114

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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.

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GABAB Receptor Signaling Pathways

Cited by 8 publications

References 65 publications

Effect ofGABABReceptor Antagonist (CGP35348) on Learning and Memory in Albino Mice

Effect ofGABABReceptor Antagonist (CGP35348) on Learning and Memory in Albino Mice

Analysis of the function of GABA_B receptors on inhibitory afferent neurons of Purkinje cells in the cerebellar cortex of the rat

The GABA Receptors

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GABAB Receptor Signaling Pathways

Cited by 8 publications

References 65 publications

Effect ofGABABReceptor Antagonist (CGP35348) on Learning and Memory in Albino Mice

Effect ofGABABReceptor Antagonist (CGP35348) on Learning and Memory in Albino Mice

Analysis of the function of GABAB receptors on inhibitory afferent neurons of Purkinje cells in the cerebellar cortex of the rat

The GABA Receptors

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Product

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Analysis of the function of GABA_B receptors on inhibitory afferent neurons of Purkinje cells in the cerebellar cortex of the rat