China
Africa
Explore chapters and articles related to this topic
Introduction: Epilepsy
Published in Candace M. Kent, David M. Chan, Analysis of a Model for Epilepsy, 2022
Candace M. Kent, David M. Chan
The metabotropic glutamate receptors, mGluRs, are divided into the following three groups, which, in turn, are divided into subtypes: Group I: subtypes 1 and 5, mGluR1 and mGluR5, respectively.Group II: subtypes 2, 3, and 4, mGluR2, mGluR3, and mGluR4, respectively.Group III: subtypes 6, 7, and 8, mGluR6, mGluR7, and mGluR8, respectively.
Pharmacotherapy of Neurochemical Imbalances
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Rupali Patil, Aman Upaganlawar, Suvarna Ingale
Glutamate receptors (Table 22.7) is composed of two families of receptors—ionotropic and metabotropic receptors. Ionotropic glutamate receptors are ion channels gated receptors which open/close upon agonist binding. Ionotropic glutamate receptors are of three types that are: N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and kainate receptors. The metabotropic glutamate receptors are: G-protein-coupled receptors. There are 11 subtypes identified (Sharma and Sharma, 2017).
ENTRIES A–Z
Published in Philip Winn, Dictionary of Biological Psychology, 2003
The first COMPLEMENTARY DNA encoding a glutamate RECEPTOR SUBUNIT (GluR1) was cloned in 1989. Molecular cloning studies have since identified a number of different subunits which can combine to form a variety of subtypes of ionotropic or metabotropic glutamate receptor channels, and IN SITU HYBRIDIZATION studies have demonstrated considerable regional variability in the expression of the constituent subunit MESSENGER RNA throughout the brain. NMDA subunits include at least seven alternatively spliced variants of NR1 (or, more cumbersomely, NMDAR1), in addition to four NR2 subunits, NR2A to NR2D; to form a functional NMDA receptor, one of the consituent subunits must be NR1. AMPA receptors are the principal mediators of fast excitatory transmission (see FAST NEUROTRANSMISSION) and can also be activated by kainic acid. They are constructed from any homomeric or heteromeric combination of two subunits GluRl to GluR4. In addition, there are at least two types of kainate receptors, which are not activated by AMPA. These are likely to be formed from HIGH AFFINITY kainate subunits such as KA1 and KA2, although these subunits themselves do not appear to form functional homomeric chan-nels. LOW-AFFINITY kainate subunits GluR5 to GluR7 share approximately 40% sequence identity with GluR1 to GluR4. There are at least 8 subtypes of metabotropic glutamate receptor, classified in subgroups according to sequence homology and on their pharmacology and transduction mechanisms when expressed in cell lines. For instance, Group 1 (mGluR1 and mGluR5) are coupled to phospholipase C.
Insights into the operational model of agonism of receptor dimers
Published in Expert Opinion on Drug Discovery, 2022
Metabotropic glutamate receptors are a member of Class C GPCRs and function as constitutive dimers. The mutation in the third intracellular loop known to prevent G-protein activation in a single protomer decreased the operational efficacy of dimers and the functional-response curve to agonist quisqualate became shallow [42]. This corresponds to OMARD where γ = 0 (one inactive subunit) and β < 1 (decreased operational efficacy of dimer binding two molecules of agonist). In agreement with experimental data, OMARD predicts a shallow functional-response curve under such conditions. Unlike Class C, Class A GPCRs may function as monomers, especially in heterologous expression systems. Their dimerization often changes their efficacy. For example, activation of one protomer by serotonin in a dimer of the 5-HT4 receptor was sufficient to increase the cAMP level. Nevertheless, coupling efficiency was two times higher upon activation of both protomers, indicating positive cooperativity in efficacy [40].
Dopaminergic and glutamatergic biomarkers disruption in addiction and regulation by exercise: a mini review
Published in Biomarkers, 2022
Muhammad Abdullah, Li-Chung Huang, Shih-Hsien Lin, Yen Kuang Yang
Repeated drug abuse also affects metabotropic glutamate receptors (Olive 2016). Among the three classes of metabotropic glutamate receptors, the most commonly explored in drug addiction are mGluR2 and mGluR5. Group II belonging mGluR2 is a presynaptic autoinhibitory receptor that acts as a negative glutamatergic modulator (Kenny and Markou 2004, Meinhardt et al.2013), while postsynaptic group I mGluR5 positively modulates glutamate transmission (Kenny and Markou 2004). Repeated intake of addictive substances causes downregulation of mGluR2 receptors, which may be responsible for the increased glutamate level (Xi et al.2002, Liechti et al.2007). Drug addiction also perturbs the mGluR5 expression in the brain. Methamphetamine has been reported to upregulate its expression in cultured brain cells (Yu et al.2001). Cocaine and other drugs have diverse results, with both increased and decreased expressions being observed (Cleva and Olive 2012). Ghasemzadeh et al. showed a decrease in mGluR5 expression associated with cocaine-seeking extinction, which predicts its linear associations with addiction, reinstatement and relapse (Ghasemzadeh et al.2009). Further studies have shown that an agonist of mGluR2 and an antagonist of mGluR5 attenuated glutamate transmission and dampened drug-associated characteristics (Cleva and Olive 2012). Together, these findings suggest that overall, addictive substances use is associated with increased glutamate transmission, either by decreasing presynaptic mGluR2 or increasing postsynaptic mGluR5 expression.
NBQX attenuates relapse of nicotine seeking but not nicotine and methamphetamine self-administration in rats
Published in The World Journal of Biological Psychiatry, 2021
Jana Ruda-Kucerova, Petra Amchova, Filip Siska, Yousef Tizabi
Recent progress in addiction’s neurobiology has identified the glutamatergic system as a significant player in various abused drugs, including nicotine (Polosa and Benowitz 2011; D’Souza 2015; Spencer and Kalivas 2017; Alasmari et al. 2018). Glutamate, a major excitatory neurotransmitter, acts on two broad categories of receptors, ionotropic and metabotropic. The ionotropic receptors are ligand-gated ion channels and are further classified into N-methyl-D-aspartate (NMDA), alpha- amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), and kainate receptors. The metabotropic receptors (mGluR), on the other hand, are G-protein coupled receptors and are further divided into eight subtypes (Karakas et al. 2015; Crupi et al. 2019). A significant amount of research has exploited the potential targeting of these receptors in drug addiction. In this regard, some recent reviews emphasise the possible use of both positive and negative allosteric modulators of metabotropic glutamate receptors in the prevention and/or treatment of drug of abuse with considerable preclinical evidence on self-administration and relapse in animals (Barnes et al. 2018; Caprioli et al. 2018; Levin et al. 2019). Besides, a role for glutamate transporters in drug addiction has been suggested (Spencer and Kalivas 2017).