Metabotropic receptor

As described in section 2.3, metabotropic receptors are divided into families, based upon second messenger mechanisms and functional effect. Group I receptors potentiate presynaptic glutamate release and NMDA receptor-mediated neurotransmission. Therapeutic effectiveness of group I agonists is therefore 

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For differentiation of G-protein-coupled receptor sub-types from subtypes permanently linked to ion channels (ligand-gated ion channels) the terms metabotropic versus ionotropic receptors, respectively, are used. Prime examples of metabotropic receptors are given by the lnGlu receptor family of G-protein-coupled glutamate receptors. 

Mesolimbic System/Reward System Metabolic Syndrome Metabotropic Glutamate Receptors Metabotropic Receptor Metalloprote(in)ases Methicillin-resistant Staphylococci iV-Methyl D-aspartate Receptors Methylating Agents... 

Despite the above precautions, it is still possible that NT spillover and extrasynaptic action may occur and indeed could be required in some instances. Thus the diffusion of glutamate beyond the synapse could activate extrasynaptic high-affinity NMDA or metabotropic receptors (Chapter 9) to produce long-lasting effects to maintain activity in a network. This may be important in long-term potentiation and memory effects. Crosstalk between synapses could also act as a back-up to ensure that a pathway functions properly (see Barbour and Hausser 1997). 

HA receptors are classified into 4 subtypes Hi, H2, H3, and H4 (Hill et al, 1997). All four HA receptor types are metabotropic receptors and belong to the superfamily of G-protein coupled receptors. Ionotropic HA receptors are found in invertebrates (Hardie, 1989 Gisselmann et al., 2002) but are absent from vertebrates (Haas Panula, 2003). Of the four HA receptors, only the Hi, H2, and H3 receptors are found in brain. The recently discovered H4 receptor is predominantly present on leukocytes and may have a critical role in the immune system (Nguyen et al., 2001 Bakker, 2004 Haas 8i Panula, 2003). 

G-protein A protein coupled to a metabotropic receptor for example, when noradrenaline binds to a p receptor it activates a Gs protein which then activates adenyl cyclase. 

Metabotropic receptor A G protein-coupled neurotransmitter receptor. 

Glutamate receptors belong to one of two main categories Ionotropic receptors are cation channels whose opening is enhanced when glutamate binds to the receptor. Metabotropic receptors do not conduct ion fluxes instead they activate intracellular enzymes through... 

V-methyl-D-aspartate receptors. Glutamate is the major excitatory neurotransmitter in the central nervous system (Ch. 15). Its receptors can be divided into three types AMPA/kainate, NMDA and metabotropic receptors. NMDA receptors are composed of two different types of subunit - NR1 and NR2. They play an important role in the induction of synaptic plasticity and excitotoxicity. 

The slow glutamate responses are mediated through metabotropic receptors coupled to G proteins 584... 

Metabotropic receptors, in contrast, create their effects by activating an intracellular G protein. The metabotropic receptors are monomers with seven transmembrane domains. The activated G protein, in turn, may activate an ion channel from an intracellular site. Alternately, G proteins work by activation or inhibition of enzymes that produce intracellular messengers. For example, activation of adenylate cyclase increases production of cyclic adenosine monophosphate (cAMP). Other effector mechanisms include activation of phospholipases, diacylglycerol, creation of inositol phosphates, and production of arachidonic acid products. Ultimately, these cascades can result in protein phosphorylation. 

A) Example of an ionotropic receptor. (B) Example of a metabotropic receptor. 

The excitatoiy amino acids (EAA), glutamate and aspartate, are the principal excitatory neurotransmitters in the brain. They are released by neurons in several distinct anatomical pathways, such as corticofugal projections, but their distribution is practically ubiquitous in the central nervous system. There are both metabotropic and ionotropic EAA receptors. The metabotropic receptors bind glutamate and are labeled mGluRl to mGluRB. They are coupled via G-proteins to phosphoinositide hydrolysis, phospholipase D, and cAMP production. Ionotropic EAA receptors have been divided into three subtypes /V-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA), and kainate receptors (Nakanishi 1992). 

Receptor-effector mechanisms include (1) enzymes with catalytic activities, (2) ion channels that gate the transmembrane flux of ions (ionotropic receptors), (3) G protein-coupled receptors that activate intracellular messengers (metabotropic receptors), and (4) cytosolic receptors that regulate gene transcription. Cytosolic receptors are a specific mechanism of many steroid and thyroid hormones. The ionotropic and metabotropic receptors are discussed in relevance to specific neurotransmitters in chapter 2. 

Ibotenate creates neurotoxic and phosphoinositide effects through distinct receptors (Zinkand et al. 1992). The neurotoxic effects are prevented by MK-801 and enhanced by glycine, implying NMDA involvement. Phosphoinositide hydrolysis is mediated by metabotropic receptors, and is unaffected by NMDA agents. 

There are two major types of receptor which are activated by neurotransmitters. These are the ionotropic and metabotropic receptors. The former receptor type is illustrated by the amino acid neurotransmitter receptors for glutamate, gamma-aminobutyric acid (GABA) and glycine, and the acetylcholine receptors of the nicotinic type. These are examples of fast transmitters in that they rapidly open and close the ionic channels in... 

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