The release of acetylcholine into the cerebral subarachnoid space of anaesthetized cats

Beleslin, D.B.; Polak, R. L.; Sproull, D. H.

doi:10.1113/jphysiol.1965.sp007601

Cited by 44 publications

(10 citation statements)

References 6 publications

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“…There is a considerable amount of evidence that this is so. Morphine reduces acetylcholine release in the isolated guinea-pig ileum (Paton, 1957;Schaumann, 1957) and in the brain Beleslin, Polak & Sproull, 1965) and the results presented in this paper are consonant with the view that, after morphine administration, acetylcholine release is reduced by a direct action of the drug rather than as a simple consequence of reduced neuronal activity. The effects of nalorphine are particularly interesting in this connection.…”

Section: Discussionsupporting

confidence: 89%

The Effect of Some Drugs on the “Free’ and “Bound” Acetylcholine Content of Rat Brain

Crossland

Slater

1968

British Journal of Pharmacology and Chemotherapy

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A number of drugs alter the acetylcholine content of the brain. In some instances the origin of this effect is clear. Thus the increase in the brain acetylcholine content which occurs during anaesthesia is probably caused by a decreased liberation of the transmitter and the similar change which follows administration of eserine is caused by the preservation of acetylcholine released in the course of normal neuronal activity. In other instances, however, it is less easy to see why the acetylcholine content has altered and it is correspondingly more difficult to determine whether the observed effect is the cause or the result of the drug's action. A study of the effects of the drug on the cholinesterase and choline acetyltransferase systems in vitro may provide additional clues but these are often insufficient to provide an answer to the question whether the action of the drug can be attributed to its intervention in the processes controlling the production, release or inactivation of acetylcholine. With these considerations in mind, an attempt has been made to obtain more information by partitioning the acetylcholine of the brain into "free " and " bound " components and determining the effects of some drugs on these acetylcholine fractions. The results of this study are presented here.No assertion is made concerning the identity of the " free " and " bound " acetylcholine fractions but the results do reveal a regularity in the response of the fractions to different types of drugs and suggest that simple fractionation of the brain acetylcholine in this way may lead to a substantial increase in our knowledge of the mode of action of centrally acting drugs.The material in this paper was the subject of a communication to the British Pharmacological Society in January, 1967. METHODSFemale Wistar rats weighing from 80 to 100 g were killed by decapitation and the excised brains were gently homogenized in ice cold normal saline solution containing eserine sulphate (15 jug/ml.) and cupric chloride (17 ,ug/ml.). The volume of medium used was 5 ml./g wet weight of brain. The homogenizer used in these experiments had a stainless steel blade rotating at a variable speed in a 15 ml. vortex flask. The speed controller on the machine was replaced by a calibrated Variac rheostat which permitted a more precise regulation of speed. Preliminary experiments had shown that with the homogenizer used a speed of 1,200 rev/min was the minimum required to obtain a thorough disintegration of brain tissue. The amount of acetylcholine extracted from the brain in these conditions rose rapidly during the first 2.5-3.0 min of homogenization and thereafter rose very slowly. * Present address: Department of Physiology, University of Manchester, Manchester 13.

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Section: Discussionsupporting

confidence: 89%

The Effect of Some Drugs on the “Free’ and “Bound” Acetylcholine Content of Rat Brain

Crossland

Slater

1968

British Journal of Pharmacology and Chemotherapy

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“…It was reported that morphine depressed the release of acetylcholine not only in iso lated guinea pig ileum (23,24) but also in the cat brain (25)(26)(27)(28). However, the recurrent inhibition via Renshaw cell arcs, relevant transmitter being considered as acetylcholine (29), was almost unchanged in our experiment by either morphine (5 mg/kg) or fentanyl (401ig/kg).…”

Section: Discussioncontrasting

confidence: 46%

Effects of Some Narcotic Analgesics Upon the Monosynaptic Reflex Inhibition From Muscular and Cutaneous Afferents in Spinal Cord of the Cat

Iwata

Sakai

1971

Jpn.J.Pharmacol

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It has been know that, at a small dose, narcotic analgesics depress polysynaptic reflex activity in the spinal cats (1) and nociccptive reflexes in the spinal rats (2), as well as in spinal cats and dogs (3-6), where they do not depress, or slightly enhace the monosynaptic reflex (3). In order to explain this depression induced by narcotic analgesics, it has been suggested that the interneurons responsible for mediation of the polysynaptic reflex are suppressed (3). Further, for a remarkable depression of nociceptive reflex discharges from high threshold cutaneous afferents by morphine and pethidine, it has been suggest ed that some interneurons activated by such small fibers of the cutaneous nerve might be inhibited (7). On the other hand, large doses of morphine (15-20 mg/kg) has been re ported to potentiate the Group la inhibition and depress the recurrent inhibition via Ren shaw cell arcs in decerebrate cats (8).
However, it remains still unknown whether narcotic analgesics may depress spinal interneurons generally or special interneurons specifically. Therefore, it was attempted in the present study to find either one of these. As a test system, the effects of some nar cotic analgesics upon the inhibitory influences to the extensor monosynaptic reflex from flexor reflex afferents were studied using unanesthetized low spinal cats. METHODSTwenty-four adult cats were used. All surgical operations were performed under ether anesthesia. After tracheal cannulation, the spinal cord was transacted between T13 and Li during local anesthesia with 1 procaine, then the lumbosacral spinal cord was exposed from L, to S After cutting the ventral roots from L, to S,, that of L, or occa sionally St was placed on the platinum wire electrode, and mono and polysynaptic re flexes evoked by stimulating the peripheral nerves were recorded from this root. The responses were projected on the cathode-ray oscilloscope (Tektronix 565).For stimulation, collar-type electrodes were placed to the following nerves of the ipsi lateral hindlimb; medial gastrocnemius-soleus, quadriceps, rural, biceps-semitendinosus (BST) and flexor digitorum longus (FDL). In addition, two pairs of the similar elect rodes were placed to the saphenous nerve for stimulating at proximal and for recording

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“…As the acetylcholine which enters the anterior horn is mainly derived from the caudate nucleus (Beleslin, Carmichael & Feldberg, 1964) the effect of morphine must be mainly on this structure. However, in experiments carried out with Dr D. H. Sproull (Beleslin, Polak & Sproull, 1965) we have found that morphine apparently has a similar effect on the cerebral cortex since it reduces the acetylcholine output into the perfused subarachnoid space. So the effect appears to be a more general one and not confined to a particular part of the brain.…”

Section: Discussionmentioning

confidence: 87%

Depression by morphine and chloralose of acetylcholine release from the cat's brain

Beleslin¹,

Polak²

1965

The Journal of Physiology

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152

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Both Paton (1957) and Schaumann (1957) have shown that morphine inhibits the release of acetylcholine from the isolated guinea-pig ileum suspended in eserinized physiological salt solution. The resting output of acetylcholine as well as the output during stimulation of the nerve endings in the intestinal wall is reduced when morphine is present in the bath fluid. According to these authors the inhibition of acetylcholine release is responsible for the paralysing action of morphine on the guinea-pig intestine. The present experiments were designed to find out whether morphine similarly depresses the release of acetylcholine from the central nervous system.When the cerebral ventricles of the cat are perfused with physiological salt solution containing an anticholinesterase acetylcholine appears in the effluent and it has recently been shown (Beleslin, Carmichael & Feldberg, 1964) that the greatest amount originates from structures lining the anterior horns of the lateral ventricles. In the present experiments therefore the method of perfusing the anterior horn of a lateral ventricle with an anticholinesterase was used to study the effect of morphine on the output of acetylcholine. In a similar way, the effect of chloralose was examined. METHODSCats of both sexes weighing between 1-8 and 3-6 kg were anaesthetized with chloralose (40-70 mg/kg) injected into the cannulated right femoral vein. To allow cannulation of the femoral vein, anaesthesia was induced with ethyl chloride and ether. The trachea was cannulated. With the cat lying on its belly the head was fixed to the ear bars and the mouthpiece of a head holder similar to that of a Horsley-Clark stereotaxic instrument. The surface of the skull was widely exposed and the muscles covering the atlanto-occipital membrane were dissected away.The anterior horn of the left lateral ventricle was perfused with neostigmine methyl sulphate in a concentration of 1/50,000. The method used was that of multiple cannulation of the ventricular system which is based on the principle that drugs perfused through one part of the ventricular system are denied access to those parts which are cannulated and perfused with artificial c.s.f. t NATO Science Fellow.

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The release of acetylcholine into the cerebral subarachnoid space of anaesthetized cats

Cited by 44 publications

References 6 publications

The Effect of Some Drugs on the “Free’ and “Bound” Acetylcholine Content of Rat Brain

The Effect of Some Drugs on the “Free’ and “Bound” Acetylcholine Content of Rat Brain

Effects of Some Narcotic Analgesics Upon the Monosynaptic Reflex Inhibition From Muscular and Cutaneous Afferents in Spinal Cord of the Cat

Depression by morphine and chloralose of acetylcholine release from the cat's brain

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