Metabotropic G protein-linked

Metabotropic G-protein linked receptors are also modulated by general anesthetics. In particular, the current produced through activation of muscarinic receptors (Ml) for acetylcholine and the serotonergic receptor 5HT2 is inhibited by halothane, isoflurane and enflurane (Lin et al., 1993 Minami et al., 1994 Durieux, 1995). Ketamine inhibits muscarinic receptors although there is no stereospecificity of inhibition (Durieux Nietgen, 1997). The S-isomer of ketamine is more potent as an anesthetic than the R-isomer (Benthuysen et al., 1989). It is thus unlikely that the Ml muscarinic receptor plays a role in... 

Ionotropic ATP receptors ATP is an excitatory NT in the central nervous system (CNS) and the peripheral nervous system (PNS). ATP acts via ionotropic, oligomeric P2X receptors that form ATP-gated Na+ and K+ channels which also have a significant permeability for Ca2+. ATP also acts via excitatory, metabotropic, G protein-linked P2Y receptors (see Chapter 5). 

It should be noted that 5HT-Rs 1, 2, 4, 5, 6 and 7 are metabotropic, G protein-linked receptors. Thus 5HT-Rs 1 and 5 inhibit adenylyl cyclase (i.e. decrease 3 -5 -cyclic adenosine monophosphate (cAMP) concentration), 5HT-R 2 increases cytosolic Ca2+ concentration and 5HT-Rs 6 and 7 stimulate adenylyl cyclase (i.e. increase cAMP concentration) as detailed in Chapter 5. 

Adenosine 5 -triphosphate is an excitatory neurotransmitter in the CNS and the peripheral nervous system (PNS). ATP acts via ionotropic P2X receptors (Chapter 3) and also acts through metabotropic G protein-linked P2Y receptors. With respect to P2Y receptors 1-13 that have been distinguished, uridine 5 -triphosphate (UTP) and ATP bind to P2Y2 and P2Y4 and ATP also binds to P2Y11. The signalling mechanism involves Gaq-mediated cytosolic Ca2+ elevation. 

However, overactivation of AMPA or KA receptors can also lead to intracellular Ca2+ overload and neurodegeneration. This maybe especially true under conditions where NMDA-receptor activity is reduced by extracellular acidity or a buildup of extracellular Zn2+ [ 12]. It is also true with respect to specific neuronal subpopulations that express AMPA-sensitive Ca2+ channels (see Ch. 15). G-protein-linked metabotropic glutamate receptors (mGluRs) appear not to mediate excitotoxicity directly but, rather, to modify the degree of excitotoxic injury. 

The NMDA, AMPA, and kainate subtypes of glutamate receptors are probably all linked to an ion channel. The metabotropic glutamate receptor subtype, however, belongs to the G protein—linked superfamily of receptors. The specific functioning of the various subtypes of glutamate receptors is the focus of intense debate. The actions at NMDA receptors will be emphasized here in our discussions on excitotoxicity. 

It should be noted that in addition to the GABA(A)-R benzodiazepine-binding sites or central benzodiazepine Rs (CBZ-Rs) there are peripheral benzodiazepine Rs (PBZ-Rs) associated with the outer membrane of mitochondria in glial cells and cells of peripheral tissue and which are involved in cholesterol transport and hence in regulation of steroid hormone synthesis. The GABA(B)-Rs are metabotropic and coupled via heterotrimeric G proteins to Ca2+ and K+ channels (Chapter 5). The psychotropic GABA breakdown product y-hydroxybutyrate (GHB) also acts via heterodimeric G protein-linked receptors (see Chapter 5). 

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. 

The metabotropic glutamate receptor family includes at least seven different types of G protein-coupled receptors (mGluRj 7). These are linked to different second messenger systems and lead to the increase of intracellular Ca or the decrease of cyclic AMP (cAMP). The increase of intracellular Ca leads to the phosphorylation of target proteins in the cell. 

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