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Biomedical subjects

L Wecker

Publications and source records attributed to L Wecker.

54 records · Page 3Linked to original sources
PubMed1982

Exogenous choline enhances the synthesis of acetylcholine only under conditions of increased cholinergic neuronal activity.

The effect choline (60 mg/kg, i.p.) on fluphenazine- and pentylenetetrazol-induced alterations in the concentration of acetylcholine (ACh) and/or the rate of sodium-dependent high-affinity choline uptake (HACU) in rat striatum and hippocampus was studied. Systemic administration of the dopamine receptor blocking agent fluphenazine hydrochloride (.05 mg/kg, i.p.) decreased the concentration of ACh in the striatum; this effect was prevented by the prior administration of choline. The central nervous system stimulant pentylenetetrazol (30 mg/kg, i.p.) reduced the concentration ACh in both striatum and hippocampus and increased the velocity of HACU in the hippocampus. Pretreatment with choline totally prevented the depletion of ACh induced by pentylenetetrazol in the striatum. In the hippocampus, prior administration of choline prevented the pentylenetetrazol-induced increase in the rate of HACU and attenuated the effect of pentylenetetrazol on the levels of ACh. Results indicate that the acute administration of choline antagonizes pharmacologically induced alterations in cholinergic activity as assessed by the rate of HACU and the steady-state concentration of ACh. Furthermore, data support the hypothesis that the administration of choline increases the ability of central cholinergic neurons to synthesize ACh under conditions of increased neuronal activity.

Acetylcholine↗
PubMed1982

Choline availability: effects on the toxicity of centrally active drugs.

The effect of chronic choline supplementation was studied on the toxicity of various pharmacological agents in rats and mice. Choline prevented both the incidence of seizures and the consequent lethality of nicotine, paraoxon, pentylenetetrazol, and strychnine. Nicotine toxicity was most markedly affected, and the prophylactic effects of choline were present in both rats and mice following either dietary or parenteral supplementation. Results suggest that chronic choline availability may alter neuronal membrane excitability.

Animals↗
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

Effects of atropine and neostigmine on receptor interaction at the neuromuscular junction.

Rats treated chronically with atropine or atropine and neostigmine showed marked alterations in the responsiveness of receptors at the neuromuscular junction. Receptors in the phrenic nerve-hemidiaphragm interacting with d-tubocurarine were unaffected by atropine but exhibited a supersensitivity after neostigmine administration. Succinylcholine-sensitive sites developed a subsensitivity with both atropine and neostigmine treatment. Acetylcholine-induced contractures in the denervated hemidiaphragm showed a hypersensitivity after both drug administrations, but responses to carbamylcholine were unaffected. It is suggested that there exists a heterogeneous population of receptors at the mammalian neuromuscular junction who can be identified by their responses to the effects of chronic drug application.

Animals↗
PubMedDate not supplied

Evidence of necrosis in human intercostal muscle following inhalation of an organophosphate insecticide.

Intercostal muscle samples obtained from autopsy of a 51 year old male, exposed to an organophosphate insecticide by inhalation, were analyzed for cholinesterase (ChE) activity and muscle fiber integrity. Muscle ChE activity, five days after exposure, was still reduced to 53% of control values. Histological analysis indicated the presence of muscle fibers with subsarcolemmal grouped granular basophilic inclusions and scattered necrotic fibers. Results indicate that acute organophosphate exposure through inhalation can lead to skeletal muscle fiber damage in humans, similar to results obtained by ingestion. Furthermore, the pathology is comparable to the histological alterations observed in rats following acute injection of organophosphates.

Diazinon↗