Chlorides pentameric

GABAa receptors are pentameric complexes on the postsynaptic membrane with a central pore with selectivity for chloride ions. Benzodiazepines and barbiturates increase the GABA-induced chloride currents, leading to hyperpolarization of the postsynaptic membrane. 

Although replacement reactions of the pentameric system are also known, these have not been as well studied (14). The following account gives a description of some of the different types of nucleophilic substitution reactions that have been well studied. The sequential replacement of chloride substituents by fluoride has been studied, and is discussed elsewhere (14, 23). 

GABAa receptors are chloride channels and members of a superfamily of ligand-gated ion channel receptors 293 A family of pentameric GABAA-receptor protein subtypes exists 294 The GABAa receptor is the major molecular target for the action of many drugs in the brain 296... 

The X-ray crystal structures of the related, though less complex, anticrown mercury-containing macrocycles 45 and 46 have also recently been reported. Complex 45 may form either 1 1 complexes with Br or I" or a 3 2 complex with Cr. In the case of the bromo derivative, crystallographic results reveal an infinite chain of alternating Br and 45 with each halide bridging between six Hg atoms, Hg- Br 3.07-3.39 A. It is postulated that the related 3 2 chloride complex exhibits a similar, though finite layered structure. The related pentameric species 46 forms... 

The GABAA receptor is now believed to be the major target site for anaesthetic action. The GABAA receptors exist as a family of subtypes with their pharmacology determined by their composition. GABAA receptors are pentameric and comprise of two a, two 3 (or 0), and one y (or s) subunits, which assemble to form a chloride-sensitive pore. When the receptor is activated, transmembrane chloride conductance increases, resulting in hyperpolarisation of the postsynaptic cell membrane and functional inhibition of the postsynaptic neurone. 

Initially, Gly was described to be restricted to the mammalian spinal cord, but subsequently it has been detected supraspinally as well (Legendre, 2001). Gly receptors (GlyRs) belong to the superfamily of receptor channels, which are generally composed of five subunits (al-4, P) (Webb and Lynch, 2007). The different a-and P-subunits are differently localized. The GlyR is a pentameric chloride channel, and it is classically known for mediating inhibitory synaptic transmission between interneurons and motor neurons in reflex circuits of the spinal cord, but they are also found presynaptically, where they modulate neurotransmitter release (Lynch, 2009 Webb and Lynch, 2007). The picture is complicated by the fact that Gly also binds to and activates NMDA receptors, therefore, it can influence the pain threshold by this action as well (see above. Section 2.3.1) (Zeilhofer, 2005). 

The tetrameric chloride is more readily hydrolyzed to the very stable acid (NH P(O)OH) 2H2O (86, 86, 88). Two octasilver salts were obtained by Stokes (88) the cyclic acid is otherwise tetrabasic. The unit cell sizes of the dihydrate, the dipotassium and dirubidium salts have have been obtained by Corbridge (15). The tetrameric acid is also formed by decomposition of the pentameric acid (90). There is little definite information on the higher acids 90, 91). 

The foregoing chemical reactions have shown the retention of the ring structure of the phosphonitrilic compounds through a variety of reactions in which the chlorine atoms are replaced by other electronegative substituents. They have chiefly concerned the trimeric and tetra-meric chlorides, because these are more abundant than the higher polymers. It is known, however, that the pentameric chloride, for instance, is both thermally stable and resistant to hydrolysis. The higher polymers have not yet been separated but the mixture of approximate composition (PNCl2)8-9 is also comparatively inert. The individual members of... 

With FeCl2, 32 gave a pentameric species shown schematically in Figure 16, in which a chloride ion is strongly bound inside the cavity. It will be noticed that the ligand strands are displaced relative to each other, so that a given pair of adjacent metal ions is linked only by two ligand strands. All five metal centres have identical chirality, A in the enantiomer shown. 

The current belief is that these receptors are pentameric and the different subunits assemble to form a chloride-sensitive pore. Stimulation of these receptors induces the opening of anionic channels (CF) which results in an inward influx of Cl (Fig. 4.3). The opening of these chatmels cause slight hyperpolarization and will resist depolarization induced by excitatory ligands. 

Fig. 22.13. Schematic representation of the y-anriinobutyric acidA (GABAa) receptor. The GABAa receptors have a pentameric structure composed predominantly of a, 3, and Y subunits arranged, in various proportions, around a central ion channel that conducts chloride. Each subunit has four membrane-spanning regions and a cysteine loop in the extracellular N-terminal domain (dashed line). The type and proportion of a and y subunit composition affects affinity, pharmacological activity, and efficacy of ligands. (Chou J. Strichartz GR, Lo EA. Pharmacology of Excitatory and Inhibitory Neurotransmission. In Golan DE, ed. Principles of Pharmacology. Philadelphia Lippincott Williams Wilkins, 2005 142 with permission.)...

Knochel s method provided the pentameric peptide 224. Hydrogenation followed by treatment of the resulting amino acid with EDC and HOBt afforded macrocycle 225. Hydrolysis of methyl ester 225, and imidazolone formation via the acid chloride, followed by Boc deprotection provided kapakahine F (219) in significant quantity. Final coupling of 219 with Boc-Phe-OH followed by Boc removal afforded kapakahine B (218) (Scheme 40). 

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