Cholinesterases of the Central Nervous System

Koelle, George B.

doi:10.1097/00005072-195501000-00003

Cited by 37 publications

(27 citation statements)

References 20 publications

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“…Such enzymes have been observed in the brains of various species (45). Eserine in low concentration inhibits cholinesterases and distinguishes them from such thiolesterases, which are not inhibited (45). Some nonspecific esterases (Type A) are inhibited by eserine in fairly high concentration, but they do not split choline esters (46).…”

Section: Discussionmentioning

confidence: 99%

The Localization of Cholinesterase Activity in Rat Cardiac Muscle by Electron Microscopy

Karnovsky

1964

The Journal of Cell Biology

488

172

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A method has been developed for localizing sites of cholinesterase activity in rat cardiac muscle by electron microscopy. The method utilizes thiocholine esters as substrates, and is believed to be dependent on the reduction of ferricyanide to ferrocyanide by thiocholine released by enzymatic activity. The ferrocyanide thus formed is captured by copper to form fine, electron-opaque deposits of copper ferrocyanide, which sharply delineate sites of enzymatic activity at the ultrastructural level. Cholinesterase activity in formalin-fixed heart muscle was localized: (a) in longitudinal elements of the sarcoplasmic reticulum, but not in the T, or transverse, elements; and (b) in the A band, with virtually no activity noted in the M band, or in the H zone. The I band was also negative. No activity was detected in the sarcolemma, or in invaginations of the sarcolemma at the level of the Z band. The perinuclear element of the sarcoplasmic (endoplasmic) reticulum was frequently strongly positive. Activity at all sites was completely abolished by omitting the substrates, or by inhibition with eserine 10-4 M and diisopropylfluorophosphate 10-5 M. Eserine 10-5 M completely inhibited reaction in the sarcoplasmic reticulum, and virtually abolished that in the A band. These observations, together with the use of the relatively specific substrates and suitable controls to eliminate non-enzymatic staining, indicate that cholinesterase activity was being demonstrated. The activity in rat heart against different substrates was that of non-specific cholinesterases, in accordance with biochemical data. The activity in the A band was considered to be probably due to myosincholinesterase. It is proposed that the localization of cholinesterases in myocardium at the ultrastructural level should be taken into account in considering the possible functions of these myocardial enzymes, and it is hoped that knowledge of their localization will open up new avenues of approach in considering their physiological role in myocardium, which at present is not definitely known.

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Section: Discussionmentioning

confidence: 99%

The Localization of Cholinesterase Activity in Rat Cardiac Muscle by Electron Microscopy

Karnovsky

1964

The Journal of Cell Biology

488

172

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“…AcChoEase is located at the same sites as well as at the plasma membranes of the preganglionic axons and their terminals (4). The localization of AcChoEase at the ganglion cell somata (1) has been assumed to account for its source at more peripheral sites in the same cells.…”

Section: Discussionmentioning

confidence: 99%

“…1 and 2) and moderate or low in the remainder; a high concentration of AcChoEase is also present in the neuropil. The latter is comprised of preganglionic axons and their terminals, ganglion cell dendrites, and Schwann sheath cells; these elements are indistinguishable by light microscopy.…”

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confidence: 95%

Identification of the probable site of synthesis of butyrylcholinesterase in the superior cervical and ciliary ganglia of the cat.

Uchida¹,

Koelle²

1983

Proc. Natl. Acad. Sci. U.S.A.

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The source of butyryicholinesterase (acylcholine acylhydrolase, EC 3.1.1.8) in the ganglion cells of the cat superior cervical and ciliary ganglia has been elusive, inasmuch as the enzyme is present in high concentrations in the neuropil, where it is confined largely to the dendritic and perikaryonal plasma mem-branes, but appears to be absent from the perikarya. In the present study, ganglionic butyrylcholinesterase was near-totally inactivated by the injection of tetramonoisopropyl pyrophosphoramide (6.0 jmol/kg of body weight) intravenously. During the ensuing 72 hr, the regenerating enzyme became detectable by the copper thiocholine histochemical method in the somata of essentially all ganglion cells and in the neuropil. Results were similar in preganglionically denervated superior cervical ganglia and in normal ciliary ganglia. These findings suggest (i) that butyrylcholinesterase indeed is synthesized in the ganglion cell perikarya (presumably, the rough endoplasmic reticulum) and transported extremely rapidly to more peripheral cellular sites and (ii) that the synthesis is largely independent of control by any neurotrophic factor provided by the preganglionic axonal terminals. Similar studies were conducted in the rat. In this species, in contrast to the cat, the somata of essentially all ganglion cells of the superior cervical ganglion contain various but at least moderate concentrations of acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) and propionylcholinesterase (acylcholine acylhydrolase, EC 3.1.1.8). After injection of tetramonoisopropyl pyrophosphoramide, propionylcholinesterase reappeared in the ganglion cell somata before its accumulation in the neuropil, as would be expected.There is a marked species difference between the cat and rat with regard to the distributions of acetylcholinesterase (AcChoEase; acetylcholine acetylhydrolase, EC 3.1.1.7) and nonspecific cholinesterase (acylcholine acylhydrolase, EC 3.1.1.8) in the superior cervical ganglion (SCG) and other autonomic ganglia.In the cat, light microscopic examination by the highly specific copper thiocholine (CuSCho) method has shown that AcChoEase is present in the perikarya of all ganglion cells of the SCG (1); its concentration there is high in a small proportion (<1%; refs. 1 and 2) and moderate or low in the remainder; a high concentration of AcChoEase is also present in the neuropil. The latter is comprised of preganglionic axons and their terminals, ganglion cell dendrites, and Schwann sheath cells; these elements are indistinguishable by light microscopy. However, more recent electron microscopic (EM) examination by the bisthioacetoxy aurate method (3) has clarified the cytological location of AcChoEase in the neuropil (4, 5). The nonspecific cholinesterase (or butyrylcholinesterase; BtChoEase) of the cat SCG appears by light microscopy to be confined to the neuropil and absent from the ganglion cell perikarya (6). It was concluded on this basis and from other studies (7, 8) that it is located in the Schwan...

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“…Diffusion of the enzyme is minimized by the incorporation of high concentrations of Na2SO, in the preincubation and incubation media (1). Specificity is assured by the use of controls containing a series of selective inhibitors (34,2). The accuracy of localization is limited by several factors, which recently have been analyzed mathematically for enzymatic histochemical methods in general by Holt and O'Sullivan (35).…”

Section: Discussionmentioning

confidence: 99%

“…Procedure D serves as a control for the detection of possible staining through the action of non-cholinesterase enzymes, adsorption of copper ion, or other non-enzymatic factors. Limitations of the specificity of the method and their control have been demonstrated by the use of additional selective inhibitors (2). Its application to tissues from other species requires preliminary determination of the appropriate concentrations of Na~SO4 and DFP (2).…”

Section: Methodsmentioning

confidence: 99%

The Cytological Localization of Intracellular Neuronal Acetylcholinesterase

Fukuda

Koelle

1959

The Journal of Cell Biology

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Sections of cat ciliary ganglia were stained for acetylcholinesterase activity by several modifications of the acetylthiocholine method in order to achieve optimal accuracy of cytological localization of the enzyme. These were compared by ordinary light and phase contrast microscopy with similar sections stained by standard techniques for Nissl substance, the Golgi apparatus, and the neurofibrillae, and by intravital methylene blue. The pattern of cytoplasmic distribution of acetylcholinesterase corresponded most closely with that of the Nissl substance. Following total inactivation of the ganglionic acetylcholinesterase by intravenously administered di-lsopropyl fluorophosphate, the reappearance of the enzyme in vlvo occurred at the same cytoplasmic sites prior to its reappearance at the cell membrane or preganglionic axonal terminations. These observations, and reports cited from the literature, provide support for the hypothesis that acetylcholinesterase is synthesized within the endoplasmic reticulum, then transported via its canaliculi to the surface of the cell and its processes, where its functional sites are oriented externally to the lipoidal membrane.It has been shown histochemically that acetylcholinesterase (ACHE) is present in relatively high concentrations throughout the entire lengths of cholinergic neurons; non-cholinergic neurons contain generally much lower concentrations (1, 2). Presently available histochemical techniques for AChE do not permit assuredly accurate, direct localization of the enzyme beyond the limits of resolution of light microscopy. However, studies of the distributions and sites of action of certain anticholinesterase (anti-ChE) agents have made possible the formulation of an hypothesis concerning the cytological localization of the enzyme. When the slowly reversible bis-quater-

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Cholinesterases of the Central Nervous System

Cited by 37 publications

References 20 publications

The Localization of Cholinesterase Activity in Rat Cardiac Muscle by Electron Microscopy

The Localization of Cholinesterase Activity in Rat Cardiac Muscle by Electron Microscopy

Identification of the probable site of synthesis of butyrylcholinesterase in the superior cervical and ciliary ganglia of the cat.

The Cytological Localization of Intracellular Neuronal Acetylcholinesterase

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