ABSTRACT
Anaphylaxis to muscle relaxants appears to be a very useful model to study the IgE-dependent mechanisms of mediator release in humans. The serum IgE binding sites of the drugs appeared to be the ammonium ion determinants. In patients allergic to suxamethonium, one of the most frequently used muscle relaxants for general anesthesia, significant histamine release could be obtained in each case with simple diammonium salts. The length of the chain linking the ammonium groups appears to play an important role. In fact, when the length was less than or equal to 4 A, no significant histamine release could be obtained, whereas the optimal length for histamine release appeared to be greater than or equal to 6 A. Furthermore, muscle relaxants with a rigid backbone between the ammonium determinants (such as pancuronium) are less active than flexible molecules (such as suxamethonium) in initiating mediator release. This study suggests that small divalent molecules can induce anaphylactic shock in sensitized patients and that the length and the flexibility of the chain bearing the haptenic determinants appear to be important factors in the elicitation of mediator release.
Subject(s)
Drug Hypersensitivity/etiology , Muscle Relaxants, Central/adverse effects , Quaternary Ammonium Compounds/physiology , Epitopes , Histamine Release/drug effects , Humans , Leukocytes/metabolism , Pancuronium/pharmacology , Quaternary Ammonium Compounds/immunology , Radioallergosorbent Test , Succinylcholine/pharmacologyABSTRACT
Spores of C. tyrobutyricum do not contain 3-phosphoglyceric acid (PGA) but a polysaccharide which could replace PGA as an energy source during germination. The absence of PGA, which is an inhibitor of phosphotransacetylase, confirms the role of the acetyl-CoA synthesizing system in the germination initiated by acetate. Spore extracts of C. tyrobutyricum, as extracts of vegetative cells, were found to contain a ferredoxin and exhibited a NADH-ferredoxin oxydase activity which required the presence of an acetyl-CoA regenerating system, suggesting that this enzyme is also involved in germination. From this results, an hypothesis on the role of initiators (acetate and NH4+) in the mechanism of initiation of spore germination in C. tyrobutyricum is proposed. Acetate would have an effect on the utilisation of the endogenous polysaccharide and on glucose catabolism, and therefore, would be an effector for the production of the energy required particularly to transport cations into the spore.
Subject(s)
Clostridium/physiology , Spores, Bacterial , Acetates/metabolism , Acetyl Coenzyme A/physiology , Energy Metabolism , Ferredoxins/metabolism , Glucose/metabolism , Glycerophosphates/metabolism , NADH, NADPH Oxidoreductases/metabolism , Phosphate Acetyltransferase/metabolism , Polysaccharides, Bacterial/metabolism , Quaternary Ammonium Compounds/physiology , ReproductionSubject(s)
Receptors, Cholinergic/drug effects , Acetylcholine/physiology , Animals , Choline/analogs & derivatives , Choline/physiology , Molecular Conformation , Muscle Relaxants, Central/pharmacology , Muscles/innervation , Parasympatholytics/physiology , Parasympathomimetics/physiology , Quaternary Ammonium Compounds/physiology , Sensory Receptor Cells/drug effects , Sensory Receptor Cells/physiology , Sensory Receptor Cells/ultrastructure , Species Specificity , Structure-Activity Relationship , Synapses/ultrastructure , Vertebrates/physiologyABSTRACT
Voltage-clamp studies on intact and internally perfused squid giant axons demonstrate that ammonium can substitute partially for either sodium or potassium. Ammonium carries the early transient current with 0.3 times the permeability of sodium and it carries the delayed current with 0.3 times the potassium permeability. The conductance changes observed in voltage clamp show approximately the same time course in ammonium solutions as in the normal physiological solutions. These ammonium ion permeabilities account for the known effects of ammonium on nerve excitability. Experiments with the drugs tetrodotoxin (TTX) and tetraethyl ammonium chloride (TEA) demonstrate that these molecules block the early and late components of the current selectively, even when both components are carried by the same ion, ammonium.
