Cross-talk and regulation between glutamate and GABAB receptors

Abstract

Brain function depends on co-ordinated transmission of signals from both excitatory and inhibitory neurotransmitters acting upon target neurons. NMDA, AMPA and mGluR receptors are the major subclasses of glutamate receptors that are involved in excitatory transmission at synapses, mechanisms of activity dependent synaptic plasticity, brain development and many neurological diseases. In addition to canonical role of regulating presynaptic release and activating postsynaptic potassium channels, GABAB receptors also regulate glutamate receptors. There is increasing evidence that metabotropic GABAB receptors are now known to play an important role in modulating the excitability of circuits throughout the brain by directly influencing different types of postsynaptic glutamate receptors. Specifically, GABAB receptors affect the expression, activity and signaling of glutamate receptors under physiological and pathological conditions. Conversely, NMDA receptor activity differentially regulates GABAB receptor subunit expression, signaling and function. In this review I will describe how GABAB receptor activity influence glutamate receptor function and vice versa. Such a modulation has widespread implications for the control of neurotransmission, calcium-dependent neuronal function, pain pathways and in various psychiatric and neurodegenerative diseases.

Effects of GABAB receptor activation on spatial cognitive function and hippocampal neurones in rat models of type 2 diabetes mellitus

“…GABAB receptors play an important part in regulating a lot of synapses including the pre- and post-synapses and are regarded as some of the most interesting targets for the treatment of numerous brain diseases, including addiction [ 8 ]. Furthermore, it is recognized that GABAB receptors are significant in regulating circuit excitability throughout the brain by directly affecting different postsynaptic glutamate receptors, that is, GABAB receptors have an influence on the activity and signaling of glutamate receptors both physiologically and pathologically [ 9 ]. In addition, according to a relevant research, there were certain occurrences involving significant alterations of the GABAB receptor density and functionality between several brain regions related to cognitive functions such as hippocampus, which would suggest that to some extent, spatial learning and memory may be associated with GABAB receptors [ 10 ].…”

The key regulator of submergence tolerance, SUB1A, promotes photosynthetic and metabolic recovery from submergence damage in rice leaves

“…Although these amino acids can also be synthesized or degraded through glutamateindependent pathways, limited induction of some amino acids in M202(Sub1) during submergence and recovery may result in part from SUB1A-mediated glutamate accumulation. It has been well documented that glutamine plays a signalling role in the mammalian central nervous system (Kantamneni 2015). In Arabidopsis, it has been shown that exogenous glutamate acts as a signalling molecule to regulate root growth and branching (Walch-Liu et al 2006;Walch-Liu & Forde 2008).…”

Progress on Active Analgesic Components and Mechanisms of Commonly Used Traditional Chinese Medicines: A Comprehensive Review

“…The various classes of flavonoids differ in the level of oxidation and the pattern of substitution of the C ring, whereas individual compounds within a class differ in the pattern of substitution of the A and B rings (11). Flavonoids (41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55) in TCM play an important role in analgesia, and have high application value and prospect.…”

“…Studies showed that the natural coumarin osthole has a variety of pharmacological effects, such as anti-tumor, anti-convulsant, antiinflammatory, osteogenic, anti-hepatitis, neuroprotective, and analgesic activities, and has a obvious effect on nucleus pulposus-evoked pain by inhibiting overexpression of acid-sensitive ion channel 3 in rat dorsal root ganglion and inhibiting the activation of extracellular signal-regulated kinase in rats (49,50) Inhibit of glutamate receptor Glutamate receptors, which are the major excitatory neurotransmitter receptors in the brain and play an important role in analgesia, has different subtypes of glutamate receptors each of which can be divided into several subtypes, such as NMDA receptors (GluN1 to GluN3), AMPA receptors (GluA1 to GluA4), kainate receptors (GluK1 to GluK5), and mGlu receptors (mGluR1 to mGluR8). Almost all types of glutamate receptors are involved in the formation of hyperalgesia (51).…”