On the origin and fate of external acetylcholinesterase in peripheral nerve.

Brimijoin, Stephen; Skau, Kenneth A.; Wiermaa, Mary Jo

doi:10.1113/jphysiol.1978.sp012563

Cited by 48 publications

(20 citation statements)

References 17 publications

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“…Serum antibody, on the other hand, was not detectable after 2 mo. Because AChE stores in nerve and muscle are replaced in a few weeks (18,19), persistent ptosis must reflect permanent cellular lesions, not mere enzyme loss.…”

Section: Resultsmentioning

confidence: 99%

Autoimmune preganglionic sympathectomy induced by acetylcholinesterase antibodies.

Brimijoin¹,

Lennon²

1990

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

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Systemic iujection of monoclonal antibodies to neural acetylcholinesterase in adult rats caused a syndrome with permanent, complement-mediated destruction of presynaptic fibers in sympathetic ganglia and adrenal medulla. Ptosis, hypotension, bradycardia, and postural syncope ensued. In sympathetic ganglia, acetyicholinesterase activity disappeared from neuropil but not from nerve cell bodies. Choline acetyltransferase activity and ultrastructurally defined synapses were also lost. Electrical stimulation of presynaptic fibers to the superior cervical ganglion ceased to evoke end-organ responses. On the other hand, direct ganglionic stimulation remained effective, and the postganglionic adrenergic system appeared intact. Motor performance and the choline acetyltransferase content of skeletal muscle were preserved, as was parasympathetic (vagal) function. This model of selective cholinergic autoimmunity represents another tool for autonomic physiology and may be relevant to the pathogenesis of human dysautonomias.At least two autoimmune disorders are caused by antibodies to exposed antigens of peripheral cholinergic synapses. In myasthenia gravis, the target is the nicotinic receptor of skeletal muscle (1-3). In the Lambert-Eaton myasthenic syndrome, it is the presynaptic voltage-gated calcium channel (4-7). Because acetylcholinesterase (AChE) is anchored in cholinergic synaptic membranes (8), this enzyme is accessible to immunoglobulins and might also be a target of autoimmunity.We recently observed long-lasting eyelid drooping (ptosis) in rats injected with monoclonal anti-AChE antibodies that neither inhibit enzymatic activity nor reach epitopes in the central nervous system in vivo (9). With these antibodies we have created a model of autoimmunity to peripheral neuronal AChE, comprising striking and permanent damage to preganglionic sympathetic neurons without evident effect on other cholinergic systems. The characteristics of this syndrome were defied by physiological, biochemical, and morphological experiments.MATERIALS AND METHODS Antibody lajections. Murine IgG monoclonal antibodies ZR 2, 3, 4, 5, and 6, raised against rat brain AChE, were purified by chromatography on DEAE-Affigel Blue (Bio-Rad) as described (10). These antibodies avidly bound all molecular forms of AChE and showed no preferences for enzyme from particular tissues. Each antibody was directed against a different epitope of AChE, but none interacted with the active site or interfered with the catalytic activity of the enzyme (10). The antibodies chosen for these experiments had no in vivo access to their epitopes on brain AChE (9). The purified IgGs were injected as an equal-part mixture (total, 1.5 mg in 2 ml of 0.9% NaCl) into the tail vein of 300-g adult male Sprague-Dawley rats. Controls received identical amounts of normal mouse IgG or a murine anti-human AChE monoclonal IgG that did not recognize rat AChE.Some rats were pretreated with cobra venom factor to deplete hemolytic complement. The protein, purified as described (11), ...

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Section: Resultsmentioning

confidence: 99%

Autoimmune preganglionic sympathectomy induced by acetylcholinesterase antibodies.

Brimijoin¹,

Lennon²

1990

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

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“…The AChE synthesized in the motor neuron is axonally transported to the presynaptic terminal as demonstrated by enzymatic and microscopic studies (Couraud and Di Giamberardino, 1980;Goemaere-Vanneste et al, 1988). Some of these enzymes may never reach nerve ending and may either be released into the extracellular spaces (Kreutzberg et al, 1973;Oh et al, 1977) or be attached to the axolemma at sites along the axon (Brimijoin et al, 1978;Li and Bon, 1983).…”

Section: Discussionmentioning

confidence: 99%

A Globular, Not Asymmetric, Form of Acetylcholinesterase Is Expressed in Chick Motor Neurons: Down‐Regulation Toward Maturity and After Denervation

Tsim

Choi

Dong

et al. 1997

Journal of Neurochemistry

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Abstract:In vertebrate neuromuscular junctions, the postsynaptic specializations include the accumulation of acetylcholinesterase (AChE) at the synaptic basal lamina and the muscle fiber. Several lines of evidence indicate that the presynaptic motor neuron is able to synthesize and secrete AChE at the neuromuscular junctions. By using anti-AChE catalytic subunit, anti-butyrylcholinesterase (BuChE) catalytic subunit, and anti-AChE collagenous tail monoclonal antibodies, we demonstrated that the motor neurons of chick spinal cord expressed AChE in vivo and the predominant AChE was the globular form of the enzyme. Neither asymmetric AChE nor BuChE was detected in the motor neurons. The molecular mass of AChE catalytic subunit in the motor neuron was~-~1O5 kDa, which was similar to that of the globular enzyme from low-salt extracts of muscle; both of them were~5 kDa smaller than the asymmetric AChE from high-salt extracts of muscle. The level of AChE expression in the motor neurons decreased, as found by immunochemical and enzymatic analysis, during the different stages of the chick's development and after nerve lesion. Thus, the AChE activity at the neuromuscular junctions that is contributed by the presynaptic motor neurons is primarily the globular, not the asymmetric, form of the enzyme, and these contributions decreased toward maturity and after denervation. Key Words: Butyryicholinesterase-Collagen-like tail-Muscle development-Neuromuscular junctions-Postsynaptic specializations.

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“…In order to eliminate any nicotinic effects that may be elicited if nicotinic ACh receptors are present in the nasal vascular ring or strip, an inhibitor of nicotinic receptor (hexamethonium 1610 -5 M) was added to the tissue bath after the washout of KCl and 30 min before a protocol began. An inhibitor of acetylcholinesterase (echothiophate 1610 -7 M) was also added [8,9]. At the end of an experiment, the maximal relaxation or passive tone of the vessel was determined by adding a maximal dose of NaNO 2 (5610 -2 M) [10].…”

Section: Tissue Bath Studiesmentioning

confidence: 99%

Acetylcholine induces contractile and relaxant effects in canine nasal venous systems

Wang¹

2006

European Respiratory Journal

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Acetylcholine (ACh) induces nasal congestion at low doses but decongestion at high doses. The current study investigated the vascular mechanisms underlying this biphasic nasal airway response in dogs.Collecting and outflow veins from anterior and posterior nasal venous systems and the septal mucosa (containing sinusoidal venous plexuses) were isolated. The in vitro isometric tension of the vascular segments was monitored to reflect vascular reactivity. Immunohistochemical localisation of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and endothelial nitric oxide synthase (eNOS) was performed.ACh did not affect the venous plexuses but contracted the anterior collecting vein and the outflow veins of both systems in a concentration-dependent manner; the responses were unaffected by nitro-L-arginine-methyl-ester (L-NAME). ACh relaxed posterior collecting veins at low concentrations but contracted them at higher concentrations; L-NAME enhanced the contractions but inhibited the relaxations, with the inhibition reversed by L-arginine. NADPHdiaphorase and eNOS were located predominantly in the posterior collecting veins.The fact that acetylcholine at low concentrations relaxes posterior collecting veins but contracts other collecting and outflow veins implies that the agonist in vivo may induce nasal congestion by increasing posterior blood volume. At higher concentrations, acetylcholine contracts posterior collecting veins as well, implying diminished blood volume in both venous systems, and consequently nasal decongestion. The induced contraction in posterior collecting veins is nitric oxide-independent, while the induced relaxation is nitric oxide-dependent.

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On the origin and fate of external acetylcholinesterase in peripheral nerve.

Cited by 48 publications

References 17 publications

Autoimmune preganglionic sympathectomy induced by acetylcholinesterase antibodies.

Autoimmune preganglionic sympathectomy induced by acetylcholinesterase antibodies.

A Globular, Not Asymmetric, Form of Acetylcholinesterase Is Expressed in Chick Motor Neurons: Down‐Regulation Toward Maturity and After Denervation

Acetylcholine induces contractile and relaxant effects in canine nasal venous systems

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