Effects of Quaternary Bases and Inorganic Cations on Acetylcholine Synthesis in Nervous Tissue

Bhatnagar, S. P.; MacIntosh, F. C.

doi:10.1139/y67-028

Cited by 88 publications

(17 citation statements)

References 4 publications

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“…This explanation is supported by the results that the synthesis was also augmented by circumferential distension when eserine was omitted from the medium and disappeared again by adding 1 x 10-8 g/ml or more ACh to the medium, and that the pre-incubated pre parations which contained a considerable amount of free ACh in the tissue failed to in crease the amount of bound ACh even when the longitudinal distension was applied. Con trol of ACh synthesis by released ACh itself in the nerve endings has been reported by Bhat nagar and Maclntosh (22) and Szerb and Somogyi (23). Potter (24) has also demonstrated that ACh is a weak competitive inhibitor of choline uptake in the presence of eserine.…”

Section: Degree Of Distension and Free Achmentioning

confidence: 67%

Changes of Tissue Acetylcholine in the Distended Intestine

Takewaki

Yagasaki

Yanagiya

1975

Japanese Journal of Pharmacology

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Abstract-The effects of distension of the intestinal wall on the liberation and the synthesis of acetylcholine (ACh) were studied in the isolated guinea-pig ileum measur ing the changes in the amount of free and bound ACh. In the presence of eserine longitudinal distension increased the amount of bound ACh in the intestinal wall without increasing the free ACh, while circumferential distension or mucosal rub bing increased free but not bound ACh. These effects were evident within 30 sec. In the eserine-free medium the amount of bound ACh was increased in either direc tion of distension. Addition of more than 5 x 10-$ g/ml ACh to the bathing medium completely blocked the distension-induced increase. It is concluded that the release and the synthesis of ACh may be both augmented by the circumferential and the longitudinal distension in the physiological conditions. In the presence of eserine, however, the presence of unphysiologically high extracellular ACh levels presumably inhibits the distension-induced augmentation of ACh synthesis in the tissue.

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Section: Degree Of Distension and Free Achmentioning

confidence: 67%

Changes of Tissue Acetylcholine in the Distended Intestine

Takewaki

Yagasaki

Yanagiya

1975

Japanese Journal of Pharmacology

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“…This was not done in the present experiments. Bhatnagar & MacIntosh (1967) pointed out that the inhibition of ACh synthesis obtained by Mann et al with excessively high KCl concentrations may have been the result of the removal of the Na from the medium, and they produced evidence in favour of this view.…”

Section: Discussionmentioning

confidence: 98%

“…A regulating negative feed-back mechanism between the ACh concentration in the tissue and the rate of ACh formation has been postulated by Mann et al (1939) on the basis of the stimulating effect of potassium, but a second negative feed-back mechanism may exist between the ACh concentration in the environment of a store of ACh and the rate of its release. In favour of such a mechanism are the recent findings that the release of ACh from minced brain (Bhatnagar & MacIntosh, 1967) and from the synaptosome fraction of a brain homogenate (Hosein, Levy & Ko, 1967) is inhibited by the addition of ACh to the medium. If ACh receptors were involved in this negative feed-back system, their sensitivity might be reduced by atropine.…”

Section: Discussionmentioning

confidence: 99%

INFLUENCE OF ANTIMUSCARINIC SUBSTANCES ON IN VITRO SYNTHESIS OF ACETYLCHOLINE BY RAT CEREBRAL CORTEX

Bertels-Meeuws

Polak

1968

British Journal of Pharmacology and Chemotherapy

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When a solution of a cholinesterase inhibitor is brought into contact with the exposed cerebral cortex or the ventricular surface of the caudate nucleus of a living animal, acetylcholine (ACh) is liberated into this fluid. There is an increase in the amount of ACh released when atropine is added to the solution or injected intravenously (Mitchell, 1963;Szerb, 1964;Polak, 1965).In the following experiments the influence of atropine and some atropine-like drugs was studied on the release and synthesis of ACh by slices of cortex from rat brain, treated with a cholinesterase (ChE) inhibitor. In certain conditions atropine was found to enhance the release of ACh from the tissue into the incubation medium and this increased release was associated with an increased synthesis of ACh. Some other antimuscarinic compounds also stimulated ACh output.Preliminary reports of some of the results of this investigation have been published elsewhere (Polak and Meeuws, 1966;Polak, 1967). METHODSFemale albino rats (160-190 g) were lightly anaesthetized with ether and decapitated. The brains were immediately removed from the skulls and placed in ice-cold oxygenated medium. In the cold room one slice in the dorsal plane was prepared from both hemispheres by means of a Stadie-Riggs microtome and weighed on a torsion balance. The thickness of the slices was about 0.5 mm. Portions of 71-208 mg of tissue were pre-incubated for 60 or 90 min at 370 C in 25 ml. vessels containing 2.5 ml. of medium to which soman (5 x10-6M) had been added in order to inactivate the ChE. Six or seven vessels with slices were incubated simultaneously. In the experiments in which pre-incubation lasted 90 min, the medium was replaced by freshly prepared medium containing soman at the end of each half hour and the tissue was rinsed once before the experiment started.In the latter type of experiments the drug under investigation was present in the medium during the last 30 min of pre-incubation.At the start of the experiment the pre-incubation medium was replaced by 2.5 or 5 ml. of medium to which extra KCI and drugs had or had not been added. At the end of the incubation period, which lasted either 60 or 30 min, the media were collected in graduated centrifuge tubes. The slices were rinsed once and then extracted with HC1 for the determination of their ACh (" total extractable ACh ") content according to the method of Elliott, Swank & Henderson (1950). The ANTIMUSCARINIC DRUGS ON CEREBRAL CORTEX washings were added to the incubation media. In many experiments one portion of tissue was extracted at the beginning of the experiment, that is immediately after pre-incubation, in order to determine the ACh content at zero-time. The extracts and media were frozen after adjusting the pH to 4 and stored until assayed for ACh.The composition of the medium was as follows (mM): NaCl, 118.5; NaHC03, 24.9; KCl, 4.7; CaC12, 2.5; KH2PO4, 1.2; MgSO4, 1.2; glucose, 10. Except when stated otherwise, soman (5 x lO-6M) was present in the medium during both pre-incubation and incubati...

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“…Based on our previous experience with (-)-vesamicol, we have now used this compound along with troxypyrrolium, an inhibitor of the nerve terminal highaffinity sodium-dependent choline uptake system (Bhatnagar & MacIntosh, 1967), to determine whether transmitter release at the rat NMJ could, as in the snake, be demonstrated to be heterogeneous. Other workers who have investigated the effects of vesamicol on transmitter release at frog (Van der Kloot, 1986;Enomoto, 1988;Lupa, 1988) and mouse (Whitton, Marshall & Parsons, 1986) NMJs have found no evidence for the heterogeneous release of more than one population of quanta.…”

Section: Introductionmentioning

confidence: 99%

Acetylcholine recycling and release at rat motor nerve terminals studied using (‐)‐vesamicol and troxpyrrolium.

Searl

Prior

Marshall

1991

The Journal of Physiology

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SUMMARY1. The presynaptic mechanisms governing the release and recycling of synaptic vesicles have been studied by examining the effects of nerve stimulation, (-)-vesamicol (an inhibitor of acetylcholine transport into synaptic vesicles) and troxypyrrolium (an inhibitor of the high-affinity, sodium-dependent, choline uptake system) on endplate currents (EPCs) and miniature endplate currents (MEPCs) recorded from motor endplates in cut rat hemidiaphragm preparations.2. In control experiments, 5 min of 10 Hz nerve stimulation had no effect on either the mean or the distribution of MEPC amplitudes.3. Nerve stimulation in the presence of (-)-vesamicol (25 nm-10 gM) revealed a population of MEPCs that was unaffected by the compound and a population of MEPCs whose mean amplitude was selectively reduced by the compound.4. Nerve stimulation in the presence of troxypyrrolium (20 ,UM) produced a uniform reduction in the amplitude of all MEPCs with no change in the coefficient of variance of MEPC amplitudes.5. The concentration-dependent effects of (-)-vesamicol on the amplitude of the evoked EPCs paralleled the concentration-dependent effects of the compound on MEPC amplitudes.6. The results are consistent with the hypothesis that both recycled and preformed synaptic vesicles are heterogeneously released from rat motor nerve terminals and that (-)-vesamicol acts selectively on recycling vesicles. In addition, a model of vesicular loading that accounts for the different effects of nerve stimulation on MEPC amplitudes in the presence of (-)-vesamicol and troxypyrrolium is described.

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Effects of Quaternary Bases and Inorganic Cations on Acetylcholine Synthesis in Nervous Tissue

Cited by 88 publications

References 4 publications

Changes of Tissue Acetylcholine in the Distended Intestine

Changes of Tissue Acetylcholine in the Distended Intestine

INFLUENCE OF ANTIMUSCARINIC SUBSTANCES ON IN VITRO SYNTHESIS OF ACETYLCHOLINE BY RAT CEREBRAL CORTEX

Acetylcholine recycling and release at rat motor nerve terminals studied using (‐)‐vesamicol and troxpyrrolium.

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