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Biomedical subjects

W D Dettbarn

Publications and source records attributed to W D Dettbarn.

At least 73 records · Page 4Linked to original sources
PubMed1978

Neuromuscular dysfunction induced by acetylcholinesterase inhibition.

The organophosphate cholinesterase inhibitor paraoxon produces a dose-dependent necrosis in rat skeletal muscle fibers after a single administration. The pathology, which is initiated at the motor end-plate region, is evident as early as 30 minutes after paraoxon administration and is characterized by dilated mitochondria, expanded sarcoplasmic reticulum, fused and widened subsynaptic folds, and coated cleft vesicles. By 24 hours, a generalized breakdown of muscle fiber architecture is evident with an accompanying infiltration of phagocytes. Electrophysiological studies have shown that paraoxon increases neurotransmitter release and causes spontaneous and impulse-related antidromic nerve activity, both of which can be reduced significantly by reactivation of inhibited acetylcholinesterase (AChE) with pyridine-2-aldoxime methiodide. The severity of the myopathy has been found to be positively correlated to the degree and duration of AChE inhibition. It appears that 2 hours of inhibition, with a critical loss in activity, viz., 85%, is necessary to initiate severe muscle fiber necrosis. Prior nerve transection prevents myopathic development and current data support the hypothesis that the induction of skeletal muscle fiber necrosis is triggered by inhibition of a neurally regulated fraction of AChE.

Acetylcholine↗
PubMed1977

Effects of atropine on paraoxon-induced alterations in brain acetylcholine.

Rats were treated acutely (one day) and chronically (seven days) with atropine, paraoxon, or both, and brain levels of acetylcholine (ACh) were determined to elucidate possible mechanisms underlying adaptation to chronic cholinesterase (ChE) inhibition. In acutely treated animals, atropine had no effect on free ACh, but decreased bound ACh levels. Conversely, paraoxon increased both free and bound ACh. Atropine pretreatment totally prevented the paraoxon-induced rise in free and bound ACh. In chronically treated animals, atropine decreased total ACh content after the initial injection, with no further changes upon subsequent administration. ACh levels increased during the first three days of paraoxon treatment, but latter injections (days 4-7) did not produce further alterations. Daily pretreatment with atropine prevented the paroxon-induced increase in ACh levels on days 1-3, but could not prevent the paraoxon-induced rise in ACh on days 4-7. Results are discussed in terms of a possible neurotransmitter accumulation, occurring under conditions of chronic ChE inhibition, that may regulate the mobilization, storage, and release of ACh.

Acetylcholine↗
PubMed1975

Cytochemical localization of cholinesterase activity at the giant synapse of the squid.

The giant synapse of squid stellate ganglion is a chemical synapse where the transmitter substance is not known. The components of the ACh-system are present in squid nervous tissue in large quantities. However externally applied cholinergic drugs have no effect on junctional transmission. Using the Copper thiocholine method for electron microscopic cytochemistry the reaction product was found at the axolemmal surface, in the cisternae of the endoplasmic reticulum of neurons and occasionally between the infoldings of the sheat cells surounding the axons. Abundant deposits of end product are observed in the extracellular space in the proximity to junctional region. However, the localization of the cytochemical end product at the junctional region proper was observed frequently, but not consistently. Radiometric measurements of enzyme activity have revealed that neither specific inhibitors nor specific substrates generaly used for differentiation of cholinesterases in mammalian nervous tissue can be employed for differentiation of squid enzymes. Considering the permeability barriers imposed for external acetylcholine by cytoplasmic processes and the high enzyme activity of structures surrounding the giant synapse, the possibility that acetylcholine may still be a candidate for the missing transmitter is discussed.

Animals↗