5′-Nucleotidase in the Nervous System

Kreutzberg, Georg W.; Heymann, D.; Reddington, Martin

doi:10.1007/978-3-642-70664-6_11

Cited by 50 publications

(35 citation statements)

References 30 publications

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“…ATP itself may be released from postganglionic nerves in the vas deferens by conditioning stimulation as discussed above. Since ATP is immediately degraded by ATPase and 5'-nucleotidase, which are ectoenzymes (Keller & Zimmermann, 1983;Nagy, Shuster & Rosenberg, 1983;Kreutzberg, Heymann & Reddington, 1986), adenosine may be produced by the enzymatic degradation of ATP as reported in excitable tissues (Ribeiro & Sebastiao, 1987).…”

Section: Involvement Of Adenosine In the Depressionmentioning

confidence: 99%

Parasympathetic depression of vas deferens contraction in the guinea‐pig involves adenosine receptors.

Kurokawa

Tsunoo

1988

The Journal of Physiology

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SUMMARY1. In the guinea-pig pelvic plexus-vas deferens preparation, stimulation of the parasympathetic pelvic nerves contracted the vas deferens then depressed the contractile responses to stimulation of the sympathetic hypogastric nerves.2. The contraction caused by stimulation of the pelvic nerves was initially phasic then tonic. The contractions were almost abolished by application of hexamethonium to the plexus. The phasic contraction was abolished by ac,-methylene adenosine triphosphate applied to the vas deferens.3. Conditioning stimulation of the pelvic nerves preferentially depressed the phasic component of test contractions evoked by hypogastric nerve stimulation but did not affect the compound action potentials in postganglionic nerves evoked by test stimulation.4. When the pelvic plexus was divided into two parts, one with the pelvic nerves and the other with the hypogastric nerves, conditioning stimulation of the pelvic nerves still depressed test contractions evoked by hypogastric nerve stimulation.5. In the de-ganglionated vas deferens preparation, conditioning stimulation of some postganglionic nerves also depressed contractions evoked by test stimulation of the other postganglionic nerves.6. 8-Phenyltheophylline (5-20,UM) applied to the vas deferens antagonized the conditioning stimulation-induced depression in both the pelvic plexus-vas deferens and the de-ganglionated preparations.7. N6-Cyclohexyladenosine (CHA) and N6-(L-2-phenylisopropyl)-adenosine at 0-5 tM preferentially inhibited phasic contractions evoked by the postganglionic nerve stimulation. The effect of CHA was antagonized by 8-phenyltheophylline (10 /bM).8. The results indicate that the mechanism underlying the conditioning stimulation-induced depression of phasic contractions operates not in the ganglia, but through activation of adenosine receptors in the vas deferens.

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Section: Involvement Of Adenosine In the Depressionmentioning

confidence: 99%

Parasympathetic depression of vas deferens contraction in the guinea‐pig involves adenosine receptors.

Kurokawa

Tsunoo

1988

The Journal of Physiology

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“…Since extracellular ATP can be converted into adenosine through the action of ecto-ATPases followed by that of ecto-5'-nucleotidase (Keller & Zimmermann, 1983;Nagy, Shuster & Rosenberg, 1983;Kreutzberg, Heymann & Reddington, 1986), it was considered of interest to know whether released ATP contributes to the pool of endogenous adenosine which modulates transmission at the neuromuscular junction.…”

Section: Introductionmentioning

confidence: 99%

On the role, inactivation and origin of endogenous adenosine at the frog neuromuscular junction.

Ribeiro

Sebastião

1987

The Journal of Physiology

146

108

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SUMMARY1. The effects of adenosine deaminase, inosine, alkylxanthines (8-phenyltheophylline (8-PT), theophylline and isobutylmethylxanthine (IBMX)), dipyridamole, a,f,-methylene ADP (AOPCP) and ATP analogues (ox,fi-methylene ATP and /,ymethylene ATP) on evoked end-plate potentials (e.p.p.s) were investigated in innervated sartorius muscles of the frog, in which twitches had been prevented with tubocurarine. The effects of 8-PT and IBMX on the amplitude and quantal content of e.p.p.s were also investigated in innervated sartorius muscles of the frog, in which twitches had been prevented with high-magnesium solutions.2. Adenosine deaminase reversibly increased the amplitude of e.p.p.s and prevented the reduction caused by exogenously applied adenosine on e.p.p. amplitude. The increase caused by adenosine deaminase was equivalent to the decrease caused by 12 + 5-8 4uM-adenosine on e.p.p. amplitude.3. Inosine, the product of adenosine deamination, was virtually devoid of effect on e.p.p.s. 4. The adenosine receptor antagonists at the frog neuromuscular junction, 8-PT and theophylline, increased in a concentration-dependent manner the amplitude of e.p.p.s in the presence of tubocurarine. 8-PT increased the amplitude and quantal content of e.p.p.s in the presence of high magnesium. IBMX, which does not behave as an adenosine receptor antagonist at the frog neuromuscular junction, decreased the amplitude of e.p.p.s in the presence of tubocurarine or high-magnesium solutions.5. Dipyridamole, an adenosine uptake blocker, decreased the amplitude of e.p.p.s, and in a concentration that did not affect neuromuscular transmission potentiated the depressing effect of adenosine, but not that of 2-chloroadenosine, on the amplitude of e.p.p.s.6. AOPCP, an inhibitor of 5'-nucleotidase, increased the amplitude of e.p.p.s and markedly attenuated the depressing effect of ATP, but not that of adenosine, on e.p.p. amplitude.7. The ATP analogue, c,,f-methylene ATP, which is not a substrate for 5'-nucleotidase, was virtually devoid of effect on e.p.p.s. fl,y-Methylene ATP, which can be a substrate for 5'-nucleotidase, mimicked the depressing effect of ATP on e.p.p. amplitude, an effect which was also reduced by AOPCP.8. It is concluded that in conditions in which the initial quantal content is assumed to be normal (1) endogenous adenosine depresses neuromuscular transmission, (2) at J. A. RIBEIRO AND A. M. SEBASTIAO the neuromuscular junction adenosine is inactivated through a dipyridamolesensitive uptake process, and (3) released adenine nucleotides might contribute to the pool of endogenous adenosine which modulates neuromuscular transmission.

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“…A major enzyme involved in catalyzing the hydrolysis of extracellular nucleoside 5′-monophosphates to the nucleoside is ecto-5′-nucleotidase [Zimmermann, 1992. This enzyme has been identified on microglial cells activated after facial nerve transection [Kreutzberg and Barron, 1978;Kreutzberg et al, 1986;Schoen et al, 1992]. These data suggest that microglia reveals an ectonucleotidase pathway capable of metabolizing ATP to adenosine.…”

Section: Enzyme Histochemistry Allocates Ectonucleotidase Activity Tomentioning

confidence: 92%

Microglial ectonucleotidases: Identification and functional roles

Braun

Zimmermann

2001

Drug Development Research

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Microglial cells represent resident macrophages of the central nervous system where they resume a resting state of unknown physiological function. They are rapidly transformed into an activated state by acute pathological events affecting the nervous system. Activated microglia function in tissue repair and regeneration but may also enhance tissue damage. Cultured microglial cells express both P2Y and P2X receptors. Activation of the microglial P2X 7 receptor can result in the release of cytokines or also mediate cytotoxicity in microglial cells. Microglial cells have developed mechanisms for controlling the surrounding concentrations of free extracellular ATP via a surface-expressed ectonucleotidase chain. We analyzed the expression of the ectonucleotidases associated with resting microglia and microglia activated by two models of cerebral ischemia. Out of a plethora of enzymes with the potential to hydrolyze extracellular nucleotides, the major ectonucleotidases associated with microglia are NTPDase1, which hydrolyzes ATP and ADP, and ecto-5′-nucleotidase, which catalyzes the hydrolysis of AMP to adenosine. This is shown by enzyme histochemical analysis, immunocytochemistry, Northern hybridization, and the analysis of NTPDase1-deficient mice. Our results suggest that a major function of resting microglia could be in the lowering of interstitial levels of ATP acting either via autocrine pathways or in the ATP-involving signaling pathways between adjacent neurons and astrocytes. Enhanced activity of NTPDase1 may protect microglia, activated by various pathological settings, from overstimulation by ATP released from the injured tissue. The parallel increase in activity of ecto-5′-nucleotidase would facilitate the formation of the final hydrolysis product adenosine that exerts neuromodulatory and immunomodulatory actions and contributes to the protection of neurons. Drug Dev. Res. 53:208-217, 2001.

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5′-Nucleotidase in the Nervous System

Cited by 50 publications

References 30 publications

Parasympathetic depression of vas deferens contraction in the guinea‐pig involves adenosine receptors.

Parasympathetic depression of vas deferens contraction in the guinea‐pig involves adenosine receptors.

On the role, inactivation and origin of endogenous adenosine at the frog neuromuscular junction.

Microglial ectonucleotidases: Identification and functional roles

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