Biomaterial Database

The influence of soman simulator on reactivation by HI-6 of soman-inhibited acetylcholinesterase in preparations of rat and human skeletal muscle. 1993

M Brank, and M Sentjurc, and A Stalc, and Z Grubic

Institute of Pathophysiology, School of Medicine, University of Ljubljana, Slovenia.

The aim of our study was to elucidate the phenomenon called "soman depot". Our investigations were focused on the depot formed in the skeletal muscle and on the effects of 1,2,2-trimethylpropyl dimethylphosphonate (PDP), a reported blocker of soman depot formation. The following questions were addressed: (1) how much of acetylcholinesterase (EC 3.1.1.7, AChE) activity can additionally be recovered by Hagedorn bispiridinium oxime reactivator 2-hydroxyimino-methylpyridinium-1-methyl-4'-carbamoyl-pyridinium-1 '-methylether dichloride monohydrate (HI-6) in the skeletal muscle preparations if they are pretreated by PDP prior to incubation in soman (1,2,2-trimethylpropyl methylphosphonofluoridate)? (2) Is this effect uniform along the muscle fibre or different in the endplate in comparison to the endplate-free region? (3) Is the effect of PDP species specific, i.e. does it differ between rat and human muscle? (4) What are the molecular mechanisms of the effects of PDP? PDP pretreatment increased the reactivation of soman-inhibited AChE by HI-6 in both regions of rat skeletal muscle. This increase was smaller in human skeletal muscle. The PDP-mediated increase in HI-6 reactivation was most efficient in the endplate-rich region of rat diaphragm as demonstrated biochemically and histochemically, but it could not be explained by the blockade of soman depot alone since it was also observed at low soman concentrations, at which soman depot is not supposed to form. This PDP effect could be better explained by the direct interactions of PDP with AChE resulting in decreased AChE phosphorylation. Soman concentration-dependent increase in HI-6 reactivation by PDP, which was more efficient at a high than a low soman concentration and could therefore originate from blockade of soman depot, was observed in the endplate-free region of rat diaphragm. It was also found in human muscle but was again smaller in this species. According to our EPR study, solubilization of soman in the lipophilic cell membrane compartment can be excluded as a mechanism producing significant soman depot. In general, our results suggest a more complex mechanism of PDP action than reported previously.

UI	MeSH Term	Description	Entries
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009045	Motor Endplate	The specialized postsynaptic region of a muscle cell. The motor endplate is immediately across the synaptic cleft from the presynaptic axon terminal. Among its anatomical specializations are junctional folds which harbor a high density of cholinergic receptors.	Motor End-Plate,End-Plate, Motor,End-Plates, Motor,Endplate, Motor,Endplates, Motor,Motor End Plate,Motor End-Plates,Motor Endplates
D009132	Muscles	Contractile tissue that produces movement in animals.	Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D010091	Oximes	Compounds that contain the radical R2C	Aldoximes,Hydroxyimino Compounds,Ketoxime,Ketoximes,Oxime,Compounds, Hydroxyimino
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D011726	Pyridinium Compounds	Derivatives of PYRIDINE containing a cation C5H5NH or radical C5H6N.	Compounds, Pyridinium
D002801	Cholinesterase Reactivators	Drugs used to reverse the inactivation of cholinesterase caused by organophosphates or sulfonates. They are an important component of therapy in agricultural, industrial, and military poisonings by organophosphates and sulfonates.	Insecticides, Organophosphate, Antagonists,Insecticides, Organothiophosphate, Antagonists,Organophosphate Insecticide Antagonists,Organothiophosphate Insecticide Antagonists,Antagonists, Organophosphate Insecticide,Antagonists, Organothiophosphate Insecticide,Insecticide Antagonists, Organophosphate,Insecticide Antagonists, Organothiophosphate,Reactivators, Cholinesterase
D002802	Cholinesterases		Acylcholineacylhydrolase,Cholase,Cholinesterase
D003964	Diaphragm	The musculofibrous partition that separates the THORACIC CAVITY from the ABDOMINAL CAVITY. Contraction of the diaphragm increases the volume of the thoracic cavity aiding INHALATION.	Respiratory Diaphragm,Diaphragm, Respiratory,Diaphragms,Diaphragms, Respiratory,Respiratory Diaphragms
D004578	Electron Spin Resonance Spectroscopy	A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as MAGNETIC RESONANCE IMAGING.	ENDOR,Electron Nuclear Double Resonance,Electron Paramagnetic Resonance,Paramagnetic Resonance,Electron Spin Resonance,Paramagnetic Resonance, Electron,Resonance, Electron Paramagnetic,Resonance, Electron Spin,Resonance, Paramagnetic