Functional acetylcholinesterase of rat diaphragm muscle

Mittag, Thomas W.; Ehrenpreis, Seymour; Hehir, Robert M.

doi:10.1016/0006-2952(71)90226-7

Cited by 31 publications

(6 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is tempting to suggest that there is enough functional acetylcholinesterase present for the animals to survive or that the functional pool of acetylcholinesterase is preferentially recovered in these animals. Although our own studies revealed a higher proportion left of the external acetylcholinesterase, suggested to represent the functional pool of the enzyme (Mittag et al 1971;Lund Karlsen & Fonnum 1977), than of the total acetylcholinesterase (table 2), it is difficult to know whether the difference between the two forms is really large enough to explain the tolerance.…”

Section: Discussionmentioning

confidence: 76%

Toxicity of Soman after Repetitive Injection of Sublethal Doses in Rat

Sterri

Lyngaas

Fonnum

1980

Acta Pharmacologica et Toxicologica

View full text Add to dashboard Cite

Injection of sublethal doses of soman in rat intraperitoneally or subcutaneously every 4, 8, 12 or 24 hours led to chronic LD50 doses which were markedly higher than the acute one. When rats were exposed every 24 hrs to half LD50 doses of soman, several of the animals did not show symptoms of soman poisoning and survived a total exposure of 4–7 times the acute LD50 dose. Brain and diaphragm acetylcholinesterase activities declined steadily during the chronic soman exposure. The so‐called external acetylcholinesterase activity of the diaphragm was inhibited to a slightly less degree than the total acetylcholinesterase of the same tissue. The ability of the liver to hydrolyze soman was similar in rats which survived several 24 hr doses and untreated rats.

show abstract

Section: Discussionmentioning

confidence: 76%

Toxicity of Soman after Repetitive Injection of Sublethal Doses in Rat

Sterri

Lyngaas

Fonnum

1980

Acta Pharmacologica et Toxicologica

View full text Add to dashboard Cite

show abstract

“…The view that functional acetylcholinesterase represents a fixed fraction of the total amount of enzyme at the neuromuscular junction (Mittag, Ehrenpreis & Hehier, 1971) is inconsistent with our findings (Table 1) which are in agreement with previous observations by Hobbiger & Lancaster (1971). However, as far as the recruitment of active enzyme sites following partial inhibition of acetylcholinesterase is concerned, it is worth mentioning that there could be differences between the in vivo situation and isolated organ preparations, as shown by Lancaster (1973) in studies of the distribution of quaternary anticholinesterases; our findings, therefore, do not necessarily faithfully duplicate the situation in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…This fraction they called functional acetylcholinesterase. Incubation of a tissue with intact cholinergic junctions is thought to limit the distribution of substrate (provided it is a quaternary compound) to the enzyme sites which are involved in the hydrolysis of acetylcholine released from nerve terminals and acetylcholinesterase activity recorded under these conditions is referred to as functional acetylcholinesterase activity (Fleischer, Hause, Killos & Harrison, 1960; Barnard & Wieckowski, 1970;Hobbiger & Lancaster, 1971;Mittag, Ehrenpreis & Hehier, 1971).…”

Section: Introductionmentioning

confidence: 99%

Relationship Between Inhibition of Acetylcholinesterase and Response of the Rat Phrenic Nerve‐diaphragm Preparation to Indirect Stimulation at Higher Frequencies

Heffron

Hobbiger

1979

British J Pharmacology

View full text Add to dashboard Cite

I Rat isolated diaphragm preparations were stimulated indirectly either intermittently at 20, 50 or 100 Hz or continuously at 0.2 Hz. 2 Addition of 1.8 gM paraoxon (which inhibits acetylcholinesterase by forming a phosphorylated enzyme which undergoes slow spontaneous reactivation) for 5 min to the organ bath produced a failure of the muscle to maintain tetanic tension (tetanic fade, Wedensky inhibition) and potentiated the neuromuscular blocking activity of exogenous acetylcholine. The rates of recovery from both these effects were recorded. 3 In a series of experiments with dyflos (which inhibits acetylcholinesterase by forming a phosphorylated enzyme which does not undergo spontaneous reactivation) the relationship between functional acetylcholinesterase activity and neuromuscular blocking activity of exogenous acetylcholine was also determined. 4 From the data obtained, the relationship between functional acetylcholinesterase activity and tetanic fade was calculated. These calculations show that (i) a considerable reduction in functional acetylcholinesterase activity is required before the diaphragm loses its ability to respond with a sustained tetanus to indirect stimulation at higher frequencies, (ii) the minimum (critical) level of functional acetylcholinesterase activity required for a normal tetanic response is directly related to the frequency of stimulation and (iii) once functional acetylcholinesterase activity has been reduced to the critical level, a very small further reduction leads to a complete tetanic fade. 5 The meaning of functional acetylcholinesterase assays and of conclusions which can be drawn . from them, is discussed,

show abstract

“…One hour after topical treatment of the eye with soman there was a striking linearity between both total and external AChE activity and pupillary diameter in the range studied. It has previously been suggested that it is the so-called external or functional AChE which is responsible for function (Mittag et al, 1971;Harris et al, 1973). In a previous report Lund Karlsen and Fonnum (1977) found that in the recovery phase from organophosphate inhibition in iris, pupillary function as determined by pupillary diameter correlated better to the return of the external part of the enzyme than to the return of the total enzyme activity.…”

Section: Discussionmentioning

confidence: 97%

Correlations Between Acetylcholinesterase Activity in Guinea‐Pig Iris and Pupillary Function: A Biochemical and Pupillographic Study

Søli

Karlsen

Opsahl

et al. 1980

Journal of Neurochemistry

View full text Add to dashboard Cite

Acetylcholinesterase (AChE) in guinea pig iris was inhibited by methylisocyclopentylfluorophosphate (soman) administered topically or parenterally, and enzyme activity was correlated to pupillary diameter by infrared pupillography. After a single topical soman instillation into the conjunctival sac there was an almost linear relationship between the reduction in AChE activity and pupillary diameter. Topical administration of soman at 24-h intervals in doses capable of almost complete inhibition of AChE in iris was accompanied by a reduced miotic effect of this drug. This was indicated by a reduced rate of the soman-induced pupillary constriction, a less pronounced reduction in pupillary diameter, and a more rapid return of the pupillary diameter to normal size. The change in pupillary diameter occurred after three daily administrations and remained constant during 31 days of treatment. These observations were seen irrespective of inhibition of blood AChE. The decrease in response to repeated administration could not be explained by a reduced inhibitory effect of soman on AChE, by a more rapid de novo synthesis of AChE, or by a change in the number of the muscarinic receptors as determined by quinuclidinyl benzilate binding. When soman or DFP was administered subcutaneously in high doses a severe AChE inhibition was obtained in iris without any concomitant miosis.

show abstract

Functional acetylcholinesterase of rat diaphragm muscle

Cited by 31 publications

References 15 publications

Toxicity of Soman after Repetitive Injection of Sublethal Doses in Rat

Toxicity of Soman after Repetitive Injection of Sublethal Doses in Rat

Relationship Between Inhibition of Acetylcholinesterase and Response of the Rat Phrenic Nerve‐diaphragm Preparation to Indirect Stimulation at Higher Frequencies

Correlations Between Acetylcholinesterase Activity in Guinea‐Pig Iris and Pupillary Function: A Biochemical and Pupillographic Study

Contact Info

Product

Resources

About