Desensitization block

Gun Propellents. Low sensitivity gun propeUants, often referred to as LOVA (low vulnerabUity ammunition), use RDX or HMX as the principal energy components, and desensitizing binders such as ceUulose acetate butyrate or thermoplastic elastomers (TPE) including poly acetal—polyurethane block copolymers, polystyrene—polyacrjiate copolymers, and glycidyl azide polymers (GAP) to provide the required mechanical... 

Anatoxin-a is the most potent and most stereospecific nicotinic acetylcholine receptor agonist thus far identified. It is also highly selective for nicotinic receptors over muscarinic receptors. The molecular parameters which influence the binding affinity, channel activation, channel blockade, and receptor desensitization are being studied. Modifications of the carbonyl and amine moieties can reduce or nearly eliminate the receptor agonist potency of the compounds and also determine the channel blocking characteristics. 

There is a definite trend of bidirectional cross-talk between opioid and chemokine receptors in the central nervous system. In vitro, as well as in vivo studies, have shown desensitization of CXCR4 by MOR and thus prevent the neuroprotective action of this chemokine. Although the precise molecular mechanism underlying this cross-talk is still under investigation, based on the evidences in literature several possible pathways can be expected to act independently or in concert and lead to the deficit of CXCR4 function. Our studies have shown that p opioids can increase the brain levels of FHC which can subsequently block CXCR4 signaling. Eurther studies... 

AMPA and kainate receptors are both blocked by quinoxalinediones but have different desensitization pharmacologies. AMPAreceptors are widespread throughout the CNS they serve as receptors for fast excitatory synaptic transmission mediated by glutamate. AMPA receptor subunits are GluRl-GluR4, kainate receptor... 

The first allosteric modulators discovered to act on AMPA/KA receptors were the plant lectins, including concanavalin A (ConA), that block receptor desensitization, probably through binding to Y-1 inked oligosaccharides (51,52). It was soon discovered that certain benzothiazides, such as diazoxide and cyclothiazide, also act on the same allosteric site controlling non-NMDA receptor desensitization (53-55). Interestingly, ConA and cyclothiazide show high selectivity for KA and AMPA receptors, respec-... 

Yamada, K. A. and Rothman, S. M. (1992) Diazoxide blocks glutamate desensitization and prolongs excitatory postsynaptic currents in rat hippocampal neurons. J. Physiol. 458, 409 123. 

Phase 1 is followed by a postdepolarization phase (phase 2) during which only the actions of nicotinic receptor agonists are blocked. This phase takes place after nicotine has acted for several minutes. At this time, the cell partially repolarizes, and its electrical excitabihty returns. The main factor responsible for phase 2 block appears to be desensitization of the receptor to ACh, which causes transmission failure. 

Although the mechanism for phase II block is not completely understood, a series of allosteric transitions in the AChR is suspected. One model to describe this has the AChR in equilibrium among four conformations resting, active, inactive, and desensitized. Agonists stabilize the active and desensitized states, whereas antagonists tend to stabilize the resting and possibly the desensitized state. 

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