Pharmacological Inhibition of Acetylcholine Synthesis

MacIntosh, F. C.; Birks, R. I.; Sastry, P. B.

doi:10.1038/1781181a0

Cited by 195 publications

(56 citation statements)

References 5 publications

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“…Thus it seems probable that hemicholinium, like hexamethonium, produces most of its blocking action on the hypogastric nerve by blocking ganglia, and not by an action on sympathetic nerve terminals, as suggested by Chang & Rand (1960) and Rand & Chang (1960). This suggestion is supported by the finding of McIntosh, Birks & Sastry (1956) that hemicholinium can cause a failure of transmission in the superior cervical ganglion of the cat. If this drug does in fact block the hypogastric nerve by an action on the ganglion cells, this may explain why it does not block the inhibitory response to sympathetic stimulation in the Finkleman preparation (Bentley, 1962), and why it does not block contractions of the nictitating membrane in response to stimulation of the postganglionic cervical sympathetic nerve in the cat (Gardiner & Thompson, 1961).…”

Section: Discussionsupporting

confidence: 76%

The Effects of Ganglion‐blocking and Postganglionic Sympatholytic Drugs on Preparations of the Guinea‐pig Vas Deferens

Bentley

Sabine

1963

British Journal of Pharmacology and Chemotherapy

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The contractions of the guinea-pig isolated vas deferens elicited by electrical stimulation of the hypogastric nerve were completely blocked by the following drugs: guanethidine, bretylium, dimethylphenylpiperazinium hydrochloride, nicotine, pempidine, hexamethonium, hemicholinium, D-tubocurarine and procaine. However, when the vas deferens was stimulated through an electrode in its lumen, the contractions in response to frequent, short stimuli (50 shocks/sec, I msec duration) were blocked by guanethidine, bretylium and dimethylphenylpiperazinium, but were not affected by the remaining drugs, except that procaine and hemicholinium each caused some reduction in the responses.When the preparation was stimulated transmurally with shocks of 200 msec duration at 1 shock/sec, the contractions were unaffected by any of the above drugs, except hemicholinium which again caused a slow reduction of up to 50% of the original response. It is concluded that nicotine, pempidine, hexamethonium, D-tubocurarine and hemicholinium probably block the response to stimulation of the hypogastric nerve by acting on peripheral ganglia in its pathway. Hemicholinium appears to have an additional effect in depressing the responses of the smooth muscle of the vas deferens to direct electrical stimulation, and procaine may act both on the ganglia and at the nerve terminals.

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Section: Discussionsupporting

confidence: 76%

The Effects of Ganglion‐blocking and Postganglionic Sympatholytic Drugs on Preparations of the Guinea‐pig Vas Deferens

Bentley

Sabine

1963

British Journal of Pharmacology and Chemotherapy

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“…Hemicholinium blocks choline uptake (e.g. MacIntosh, Birks & Sastry, 1956;Schuberth, Sundwall, Sorbo & Lindell, 1966;Marchbanks, 1968;Diamond & Milfay, 1972) but has little effect on ACh release (Birks & MacIntosh, 1961;Matthews, 1966;Takagi, Kojima, Nagata & Kuromi, 1970). It seems likely, therefore, that under the conditions of the present experiments, neostigmine does not enhance ACh release.…”

Section: Discussionmentioning

confidence: 99%

Acetylcholine synthesis from recaptured choline by a sympathetic ganglion

Collier¹,

Katz²

1974

The Journal of Physiology

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SUMMARY1. The recapture and re-use of choline formed by the hydrolysis of released acetylcholine (ACh) nerve terminals appear selectively to accumulate choline. 4. However, chronically decentralized ganglia accumulated as much choline as did acutely decentralized ganglia, and this was interpreted as indicating that at rest preganglionic nerve terminals do not selectively accumulate choline.5. Increased exogenous choline concentration increased the amount of radioactivity collected during nerve stimulation in the absence, but not the presence, of an anticholinesterase agent. The spontaneous efflux of radioactivity was little affected by changes in external choline levels. It is concluded that exogenous choline and choline made available from released transmitter compete for uptake into nerve terminals.

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“…Hemicholinium has proved useful in investigating the course of synthesis of acetylcholine. Schueler (1955) first suggested that hemicholinium-3 might interfere with cholinergic mechanisms, and later this compound was shown to inhibit acetylcholine synthesis in the cat superior cervical ganglion (MacIntosh, Birks & Sastry, 1956). A currently accepted hypo-thesis postulates that hemicholinium prevents the transport of choline from the extracellular fluid to the point of acetylation (Gardiner, 1957;MacIntosh, 1961).…”

mentioning

confidence: 99%

The Origin of the Acetylcholine Released Spontaneously From the Guinea‐pig Isolated Ileum

Johnson

1963

British Journal of Pharmacology and Chemotherapy

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When the guinea-pig isolated ileum had been previously treated with the anticholinesterase, NN-diisopropylphosphodiamidic fluoride (mipafox), and attached to an isotonic lever loaded with 0.5 g, it released acetylcholine into Krebs solution gassed with a mixture of 95% oxygen and 5% carbon dioxide. The amount of acetylcholine spontaneously released depended on the duration of the rest period. Cocaine, procaine or cooling the preparation to 25°C greatly reduced this spontaneous output of acetylcholine, thus providing evidence in support of nervous origin of the ester. Reduction of the calcium ion content of the Krebs solution to one-twentieth of its usual value or increase in the magnesium ion content four-fold, changes which inhibit the release of acetylcholine from somatic motor nerve-endings, inhibited the output of acetylcholine from the ileum. When all the calcium of Krebs solution had been replaced by strontium one-third of the control output of acetylcholine was obtained, but the smooth muscle of the guinea-pig ileum would not respond to drugs under these conditions. Strontium could thus partially substitute for calcium in nerves but not in muscle. Hemicholinium-3 (100 jug/ml.) inhibited the spontaneous release of acetylcholine and 400 jug/ml. of choline was required to reverse the inhibition. It is concluded that cocaine, procaine, cooling, reduction of calcium ion and increase of magnesium ion concentrations all reduce the spontaneous output of acetylcholine, which has its origin in the parasympathetic nerve-endings of the intramural nerve plexuses. Further, the hemicholinium experiments seem to justify the conclusion that the release of acetylcholine is reduced because synthesis is reduced.

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Pharmacological Inhibition of Acetylcholine Synthesis

Cited by 195 publications

References 5 publications

The Effects of Ganglion‐blocking and Postganglionic Sympatholytic Drugs on Preparations of the Guinea‐pig Vas Deferens

The Effects of Ganglion‐blocking and Postganglionic Sympatholytic Drugs on Preparations of the Guinea‐pig Vas Deferens

Acetylcholine synthesis from recaptured choline by a sympathetic ganglion

The Origin of the Acetylcholine Released Spontaneously From the Guinea‐pig Isolated Ileum

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