L-glutamic acid, a neurotrophic factor for maintenance of acetylcholinesterase and butyrylcholinesterase in the preganglionically denervated superior cervical ganglion of the cat.

Koelle, George B.; Sanville, Ursula J.; Thampi, Nagendran S.; Wall, Stephen

doi:10.1073/pnas.83.8.2751

Cited by 23 publications

(8 citation statements)

References 37 publications

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“…The present study complements other observations of apparent trophic actions of glutamate. For example, intra-arterial infusion of glutamate opposes the decrease of esterase activity that occurs in mammalian autonomic ganglia on denervation (Koelle et al, 1986). It has also been reported that glutamate (at 5 pM) promotes the growth and differentiation of rat whole brain cultures (Aruffo et al, 1987), whereas stimulation of NMDA receptors promotes both survival and neurite outgrowth in rat cerebellar cultures (Pearce et al, 1987;Balazs et al, 1988a,b).…”

Section: Discussionmentioning

confidence: 96%

Sprouting by isolated Helisoma neurons: Enhancement by glutamate

Bulloch

Hauser

1990

Intl J of Devlp Neuroscience

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We tested glutamate for its ability to modulate neurite outgrowth from isolated neurons of the adult snail, Helisoma trivolvis. Although glutamate did not induce neurite outgrowth from neurons maintained in defined medium, nevertheless it showed a dose-dependent ability to enhance the activity of conditioned medium. We concluded that glutamate can enhance the release and/or activity of CNS derived sprouting factor(s) present in conditioned medium. The general conclusion to be drawn from this study is that the ability of a neurotrophic factor(s) to promote neurite outgrowth can be regulated by a neurotransmitter. This mechanism may be important in the regulation of trophic factors in the adult nervous system.

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Section: Discussionmentioning

confidence: 96%

Sprouting by isolated Helisoma neurons: Enhancement by glutamate

Bulloch

Hauser

1990

Intl J of Devlp Neuroscience

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“…In a recent series of experiments (1,(3)(4)(5)(6) it was shown that the 24-hr intracarotid infusion of a dialyzed aqueous extract of cat brain, spinal cord, and sciatic nerves, or of glycyl-L-glutamine (Gly-Gln), or of some closely related compounds, opposes the decrease of both enzymes. Gly-Gln was tested after the demonstration by Haynes and Smith (7) that this compound increases the formation of the G4 (globular tetramer) and A12 (collagen-tailed, asymmetric dodecamer) forms of AcChoEase (8) in cultured preparations of embryonic rat and chicken skeletal muscle.…”

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confidence: 99%

Effects of glycyl-L-glutamine in vitro on the molecular forms of acetylcholinesterase in the preganglionically denervated superior cervical ganglion of the cat.

Koelle¹,

Massoulié²,

Eugène³

et al. 1988

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

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Normal and preganglionically denervated cat superior cervical ganglia were sectioned and cultured for 24 or 48 hr, with or without preliminary inactivation of acetylcholinesterase, and in the presence or absence of 10-5 M glycyl-L-glutamine. They were then homogenized, and the molecular forms of acetylcholinesterase were analyzed by sucrose gradient sedimentation. We observed an increased proportion of the globular monomeric G, form, and to a lesser extent of the dimeric G2 and tetrameric membranous G4 forms, of acetylcholinesterase in the glycyl-L-glutamine-treated compared with the control cultures. There was only a small increase in the total acetylcholinesterase activity and no significant variation in the activity of the metabolic enzyme lactate dehydrogenase. It therefore seems likely that glycyl-L-glutamine, or the endogenous neurotrophic factor, maintains acetylcholinesterase in the preganglionically denervated ganglia in vivo by specifically increasing the biosynthesis of the monomeric G, form, but not that of other proteins; these trophic factors do not seem to promote the polymerization of G, into the more complex G2 and G4 forms.Preganglionic denervation of the cat superior cervical ganglion (SCG) results within a few days in a marked decrease in its contents of acetylcholinesterase (AcChoEase, EC 3.1.1.7) and butyrylcholinesterase (BtChoEase, EC 3.1.1.8) (1, 2). In a recent series of experiments (1, 3-6) it was shown that the 24-hr intracarotid infusion of a dialyzed aqueous extract of cat brain, spinal cord, and sciatic nerves, or of glycyl-L-glutamine (Gly-Gln), or of some closely related compounds, opposes the decrease of both enzymes. Gly-Gln was tested after the demonstration by Haynes and Smith (7) that this compound increases the formation of the G4 (globular tetramer) and A12 (collagen-tailed, asymmetric dodecamer) forms of AcChoEase (8) in cultured preparations of embryonic rat and chicken skeletal muscle.In the present study we investigated the stage at which Gly-Gln, or the unidentified endogenous neurotrophic factor, enhances the production of AcChoEase in denervated ganglia. In an effort to study this effect in vitro, we first used whole desheathed rat SCG that had been preganglionically denervated one day previously. Results were suggestive, but equivocal, probably for the reasons given in the Discussion and, consequently, are not presented.In the experiments reported here, sections of normal or preganglionically denervated cat SCG were incubated in culture medium for 24 or 48 hr, with or without inactivation of their initial AcChoEase content, and with or without the addition of Gly-Gln or nervous tissue extract. The SCGs were then homogenized in a high-salt and Triton X-100-containing extraction medium to solubilize AcChoEase. The molecular forms of the enzyme were analyzed by sedimentation in sucrose density gradients, as described previously (9). METHODSWe cultured sections of cat SCG with a number of variations: the interval between preganglionic denervation and excision, ...

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“…Of the possible candidates tested, glycine and Lglutamine were found to be inactive, but glycyl-L-glutamic acid (Gly-Glu) was moderately active at both the right and left SCG (6). It was shown subsequently that L-glutamic acid has a similar effect, whereas pyroglutamic acid, aspartic acid, and -y-aminobutyric acid were inactive (7). However, neither Gly-Glu nor L-glutamic acid, over a wide range of concentrations, was as effective in preventing the fall in AcChoEase at the right or left SCG as was Gly-Gln at the left SCG following infusion into the right common carotid artery.…”

mentioning

confidence: 92%

Direct neurotrophic action of glycyl-L-glutamine in the maintenance of acetylcholinesterase and butyrylcholinesterase in the preganglionically denervated superior cervical ganglion of the cat.

Koelle¹,

Sanville²,

Thampi³

1987

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

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Intracarotid infusion of glycyl-L-glutamine (Gly-Gln) was shown previously to oppose the fall in the acetyicholinesterase and butyrylcholinesterase contents of the cat superior cervical ganglion (SCG) that otherwise follows preganglionic denervation. However, its effect was demonstrable only on the vasculary remote left SCG but not on the directly infused right SCG. Accordingly, it was concluded that a metabolite of Gly-Gln, formed in the blood, is an active neurotrophic factor. Glycyl-L-glutamic acid and L-glutamic acid were subsequently found to have a similar but less marked effect on both SCG. In the present study an alternative explanation has been tested: that Gly-Gln must combine slowly with some component of plasma to enable it to penetrate the ganglion cells and exert its neurotrophic effect. Findings are consistent with the latter proposal.The fall in the acetylcholinesterase (AcChoEase, EC 3.1.1.7) and butyrylcholinesterase (BtChoEase, EC 3.1.1.8) contents of the cat superior cervical ganglion (SCG) that follows preganglionic denervation (1, 2) is opposed by the intracarotid infusion of an aqueous extract of cat brain, spinal cord, and sciatic nerves (3) or its dialysate (Mr cutoff, 1000) (4). Following a report that glycyl-L-glutamine (Gly-Gln) showed a similar effect on cultured rat and chicken skeletal muscle (5), this compound was tested in the cat preparation. It was found to be ineffective at the directly infused right SCG but highly active in maintaining AcChoEase and BtChoEase at the circulatory remote left SCG (6). It was therefore concluded that a metabolite of Gly-Gln, formed in the blood, is a direct neurotrophic factor for the production of this effect. Of the possible candidates tested, glycine and Lglutamine were found to be inactive, but glycyl-L-glutamic acid (Gly-Glu) was moderately active at both the right and left SCG (6). It was shown subsequently that L-glutamic acid has a similar effect, whereas pyroglutamic acid, aspartic acid, and -y-aminobutyric acid were inactive (7). However, neither Gly-Glu nor L-glutamic acid, over a wide range of concentrations, was as effective in preventing the fall in AcChoEase at the right or left SCG as was Gly-Gln at the left SCG following infusion into the right common carotid artery.Here we have tested an alternative explanation for the restriction of the neurotrophic action of Gly-Gln to the left SCG under the above conditions: that Gly-Gln combines relatively slowly with a component of plasma to permit its penetration to the cytoplasm of the neurons of the SCG. In contrast with Gly-Glu and L-glutamic acid, which are relatively lipid soluble, Gly-Gln is a highly polar compound and hence its permeation of the cell membrane should be limited. Lowry et al. (10).Heparinized blood was obtained from experimental cats by intracardiac puncture immediately following sacrifice; it was centrifuged on a Dynac centrifuge at 3500 rpm for 30 min at 5°C, and the plasma was removed and frozen until use. In the initial experimental series, freshly prepar...

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L-glutamic acid, a neurotrophic factor for maintenance of acetylcholinesterase and butyrylcholinesterase in the preganglionically denervated superior cervical ganglion of the cat.

Cited by 23 publications

References 37 publications

Sprouting by isolated Helisoma neurons: Enhancement by glutamate

Sprouting by isolated Helisoma neurons: Enhancement by glutamate

Effects of glycyl-L-glutamine in vitro on the molecular forms of acetylcholinesterase in the preganglionically denervated superior cervical ganglion of the cat.

Direct neurotrophic action of glycyl-L-glutamine in the maintenance of acetylcholinesterase and butyrylcholinesterase in the preganglionically denervated superior cervical ganglion of the cat.

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