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Introduction: Epilepsy
Published in Candace M. Kent, David M. Chan, Analysis of a Model for Epilepsy, 2022
Candace M. Kent, David M. Chan
There are two types of receptors for the neurotransmitter glutamate, as well as for other neurotransmitters. They are the ionotropic glutamate receptors, iGluRs, and the metabotropic glutamate receptors, mGluRs. An ionotropic receptor is directly linked to an ion channel, and upon binding to the neurotransmitter quickly opens up the ion channel to the selective passage of ions into or out of the neuronal cell [3], [42]. The ionotropic receptors are said to mediate the neurotransmitters that they bind to [23]. A metabotropic receptor is indirectly linked, through a series of steps in a biochemical pathway, to an ion channel and upon binding to the neurotransmitter more slowly opens up the ion channel [3], [42]. The metabotropic receptors are said to modulate the neurotransmitters they bind to [23].
Developmental Changes in the Respiratory System of the Neonate-Child
Published in Susmita Chowdhuri, M Safwan Badr, James A Rowley, Control of Breathing during Sleep, 2022
Ahuva Brown, Liran Tamir Hostovsky, Estelle B Gauda
In the brain, gamma-aminobutyric acid (GABA) and glycine are the major inhibitory neurotransmitters, while the major excitatory neurotransmitter is glutamate. They bind to inotropic receptors that are fast-acting ligand-gated ion channels and to metabotropic receptors that initiate intracellular signaling by G-proteins activation (Figure 3.4).
Brainstem and Cardiovascular Regulation
Published in David Robertson, Italo Biaggioni, Disorders of the Autonomic Nervous System, 2019
Ching-Jiunn Tseng, Che-Se Tung
It has been suggested that glutamate or a closely related excitatory substance is an important neurotransmitter of baroreceptor afferents terminating in the NTS (Taiman, Perrone and Reis, 1980). Microinjection of glutamate or its analogs into the NTS evokes a dose-dependent fall in arterial blood pressure, bradycardia, and apnea (Taiman, Perrone and Reis, 1980). Administration within the NTS of glutamate receptor antagonists, such as glutamate diethylester (GDEE) or kynurenic acid, increased arterial pressure and blunted baroreflex activation (Taiman et al., 1980; Leone and Gordon, 1989). The nature of the glutamate receptor involved in the baroreflex arc and in the responses to glutamate is still under discussion. Both NMDA and non-NMDA receptors (including the metabotropic receptor) have been implicated.
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
Receptor-level perturbations in the glutamatergic system may affect the ionotropic and metabotropic receptors (Olive 2016). Glutamatergic ionotropic receptor modulations promote drug-related behaviours by targeting neurobiological mechanisms (e.g. LTP/LTD and dendritic spines head diameter) associated with drug addiction (Volkow and Morales 2015). The relations that connect drug-associated memories, reward pathways-strengthening, and relapse indicate the roles of ionotropic NMDA and AMPA receptors. A study by Gipson et al., a comprehensive animal work, demonstrated overall glutamatergic system modulation, with upregulation of AMPA and NMDA receptors, and glutamate overflow in nicotine addiction (Gipson et al.2013). AMPA and NMDA receptor redistribution and density modulation have also been observed in other types of addiction (Fitzgerald et al.1996, Carlezon and Nestler 2002, Guo et al.2009, Kalivas 2009).
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).
Glutamatergic dysregulation in mood disorders: opportunities for the discovery of novel drug targets
Published in Expert Opinion on Therapeutic Targets, 2020
Panek Małgorzata, Kawalec Paweł, Malinowska Lipień Iwona, Tomasz Brzostek, Pilc Andrzej
Metabotropic receptors are G protein–coupled receptors that, unlike inotropic receptors, do not form an ion channel. They are built of a polypeptide chain that crosses the cell membrane seven times, creating three extracellular and three intracellular loops [28]. Based on the mutual similarity of the amino-acid sequences and a similar pharmacological profile, mGlu receptors are divided into three subgroups: group I receptors (mGlu1 and mGlu5), which are positively coupled to phospholipase C as well as group II receptors (mGlu2 and mGlu3) and group III receptors (mGlu4, mGlu6, mGlu7, and mGlu8), which are negatively coupled to adenylate cyclase [37]. Metabotropic receptors have a huge therapeutic potential. They are located in most brain structures and on almost all types of neurons. They may be also located on nerve cell bodies and may regulate the activity of the neuron. Such expression is typical for group I receptors. The receptors may be also bound by intercellular Homer and Shank proteins to the ionotropic NMDA receptor, which from a pharmacological point of view, may lead to adverse effects typical for the stimulation/blockade of the NMDA receptor. Groups II and III mGluR receptors are located mainly on the endings of axons. Such a location allows the receptors to control neurotransmitter release [33,35].