ABSTRACT
A temporal and causal relationship has been established between inhibition of acetylcholinesterase (AChE) by organophosphorous compounds, accumulation of Ca2+, an increase of neutral protease activity and the development of the ultrastructural signs of subacute myopathy.
Subject(s)
Calcium/metabolism , Muscular Diseases/chemically induced , Organophosphorus Compounds/toxicity , Peptide Hydrolases/metabolism , Acetylcholinesterase/metabolism , Animals , Histocytochemistry , Isoflurophate/toxicity , Motor Endplate/enzymology , Muscles/ultrastructure , Muscular Diseases/metabolism , Rats , Rats, Inbred StrainsABSTRACT
The histochemical changes occurring in association with the development of acute and subacute myopathy have been studied in the rat diaphragm 30 min-48 h after a single i.p. injection of 1.82 mg/kg of the irreversible cholinesterase inhibitor organophosphate, diisopropylfluorophosphate (DFP). In addition to a considerable inhibition of the AChE activity of the motor end-plates, accumulation of ionic Ca2+ and an increase in neutral protease activity in the subjunctional sarcoplasm have been demonstrated. A temporal and causal relationship has been established between the histochemical changes and the development of the ultrastructural signs of myopathy.
Subject(s)
Isoflurophate/pharmacology , Muscular Diseases/pathology , Acute Disease , Animals , Calcium/metabolism , Cholinesterase Inhibitors , Diaphragm/metabolism , Histocytochemistry , Microscopy, Electron , Muscular Diseases/chemically induced , Peptide Hydrolases/metabolism , RatsABSTRACT
A single subcutaneous injection of monosodium-L-glutamate induces severe ultrastructural alterations in certain AChE positive parenchymal cells of the Area postrema of the adult rat. Signs of cellular degeneration include massive intracellular edema, swelling of mitochondria, vacuolization of the cisternae of the rough endoplasmic reticulum and marked alterations in the chromatin pattern of the nucleus. Identification of these cells as neurons is based on the presence of axosomatic synapses.
Subject(s)
Brain/ultrastructure , Glutamates/pharmacology , Neurons/ultrastructure , Sodium Glutamate/pharmacology , Animals , Chromatin/ultrastructure , Microscopy, Electron , Neurons/drug effects , RatsABSTRACT
In the site of the myoneural junction a liberation of Ca++ ions, which is similar to that described previously after an electric stimulation or use of cholinesterase inhibitor, can be revealed by histochemical methods (heavy metal substitution, tetracycline fluorescence technique and glyoxal-bis-(2-hydroxyanil) complex formation) using repeated acetylcholine and SCh administration. The possible aspecific reaction due to the presence of Mg++ ions can be excluded by means of the glyoxal-bis(2-hydroxyanil) method. It can be suggested that there is a correlation between the liberation of Ca++ ions an the function dependent mitochondrial energetic processes.
Subject(s)
Acetylcholine/pharmacology , Calcium/metabolism , Diaphragm/drug effects , Neuromuscular Junction/drug effects , Animals , Diaphragm/innervation , Diaphragm/metabolism , Histocytochemistry/methods , Neuromuscular Junction/metabolism , Rats , Succinylcholine/pharmacologyABSTRACT
Authors studied the proteolytic enzyme activity of motor end plates in the diaphragms and M. flexor digitorum brevis of rats after administration of cholinesterase inhibitors and after supramaximal electric stimulation, using the colour film digestion technique. Enhanced enzyme activity characterizing stimulated motor end plates persisted up to 12 h after stimulation. No proteolytic activity could be shown any more 24 h after stimulation, indicating restoration of the resting state. The role of metabolites (oligopeptides and amino-acids) released by the function-dependent axoterminal proteolysis is discussed in relation to neurochemical transmission processes.
