S-adenosyl-l-methionine modulates firing rate of dorsal motor nucleus of the vagus neurones in vitro

Renato Alberto Travagli, Richard A. Gillis, Kenneth J. Kellar

Research output: Contribution to journalArticle

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Abstract

We used the patch clamp technique applied to an in vitro brain slice preparation to examine the changes in firing activity of single dorsal vagal motoneurones exposed to S-adenosyl-methionine. In approximately 70% of the neurones tested, S-adenosyl-l-methionine (1-100 μM) decreased the spontaneously occurring firing in a dose dependent manner; the plateau decrease was 40±6%. The peak effect was observed approximately 5 min after the superfision with S-adenosyl-l-methionine was started, and was usually reversible upon wash out of S-adenosyl-l-methionine from the superfusing chamber. No effect of the control salt of S-adenosyl-l-methionine, 1,4-butane-disulfonate·Na (100 μM), was observed. The frequency of discharge observed upon depolarization steps from hyperpolarized potentials was reduced to 34±17% (n=11) of control upon S-adenosyl-l-methionine (100 μM) superfusion; no effect of S-adenosyl-l-methionine was observed on the action potential threshold. Preincubation with adenosine receptor antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 10 nM) and 3,7-dimethyl-1-propargylxanthine (DMPX, 50 μM), reversed the S-adenosyl-l-methionine-induced inhibition of firing rate, and in fact, in the presence of these adenosine antagonists, S-adenosyl-l-methionine increased the firing rate of vagal motoneurones. This excitation of vagal motoneurones was blocked by pretreatment with S-adenosyl-homocysteine (100 μM), an inhibitor of methylation reactions. It is concluded that the inhibitory activity of S-adenosyl-l-methionine on the firing rate of vagal motoneurones is due to its metabolic transformation into adenosine which then acts on adenosine receptors. The excitatory effect on firing rate appears to be due to other actions, possibly including methylation reactions of key components of signal transduction mechanisms.

Original languageEnglish (US)
Pages (from-to)385-390
Number of pages6
JournalEuropean Journal of Pharmacology
Volume264
Issue number3
DOIs
StatePublished - Nov 3 1994

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Methionine
Neurons
Motor Neurons
Adenosine
Methylation
In Vitro Techniques
Purinergic P1 Receptor Antagonists
Purinergic P1 Receptors
Homocysteine
Patch-Clamp Techniques
Action Potentials
Signal Transduction
Salts
Brain

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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title = "S-adenosyl-l-methionine modulates firing rate of dorsal motor nucleus of the vagus neurones in vitro",
abstract = "We used the patch clamp technique applied to an in vitro brain slice preparation to examine the changes in firing activity of single dorsal vagal motoneurones exposed to S-adenosyl-methionine. In approximately 70{\%} of the neurones tested, S-adenosyl-l-methionine (1-100 μM) decreased the spontaneously occurring firing in a dose dependent manner; the plateau decrease was 40±6{\%}. The peak effect was observed approximately 5 min after the superfision with S-adenosyl-l-methionine was started, and was usually reversible upon wash out of S-adenosyl-l-methionine from the superfusing chamber. No effect of the control salt of S-adenosyl-l-methionine, 1,4-butane-disulfonate·Na (100 μM), was observed. The frequency of discharge observed upon depolarization steps from hyperpolarized potentials was reduced to 34±17{\%} (n=11) of control upon S-adenosyl-l-methionine (100 μM) superfusion; no effect of S-adenosyl-l-methionine was observed on the action potential threshold. Preincubation with adenosine receptor antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 10 nM) and 3,7-dimethyl-1-propargylxanthine (DMPX, 50 μM), reversed the S-adenosyl-l-methionine-induced inhibition of firing rate, and in fact, in the presence of these adenosine antagonists, S-adenosyl-l-methionine increased the firing rate of vagal motoneurones. This excitation of vagal motoneurones was blocked by pretreatment with S-adenosyl-homocysteine (100 μM), an inhibitor of methylation reactions. It is concluded that the inhibitory activity of S-adenosyl-l-methionine on the firing rate of vagal motoneurones is due to its metabolic transformation into adenosine which then acts on adenosine receptors. The excitatory effect on firing rate appears to be due to other actions, possibly including methylation reactions of key components of signal transduction mechanisms.",
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S-adenosyl-l-methionine modulates firing rate of dorsal motor nucleus of the vagus neurones in vitro. / Travagli, Renato Alberto; Gillis, Richard A.; Kellar, Kenneth J.

In: European Journal of Pharmacology, Vol. 264, No. 3, 03.11.1994, p. 385-390.

Research output: Contribution to journalArticle

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N2 - We used the patch clamp technique applied to an in vitro brain slice preparation to examine the changes in firing activity of single dorsal vagal motoneurones exposed to S-adenosyl-methionine. In approximately 70% of the neurones tested, S-adenosyl-l-methionine (1-100 μM) decreased the spontaneously occurring firing in a dose dependent manner; the plateau decrease was 40±6%. The peak effect was observed approximately 5 min after the superfision with S-adenosyl-l-methionine was started, and was usually reversible upon wash out of S-adenosyl-l-methionine from the superfusing chamber. No effect of the control salt of S-adenosyl-l-methionine, 1,4-butane-disulfonate·Na (100 μM), was observed. The frequency of discharge observed upon depolarization steps from hyperpolarized potentials was reduced to 34±17% (n=11) of control upon S-adenosyl-l-methionine (100 μM) superfusion; no effect of S-adenosyl-l-methionine was observed on the action potential threshold. Preincubation with adenosine receptor antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 10 nM) and 3,7-dimethyl-1-propargylxanthine (DMPX, 50 μM), reversed the S-adenosyl-l-methionine-induced inhibition of firing rate, and in fact, in the presence of these adenosine antagonists, S-adenosyl-l-methionine increased the firing rate of vagal motoneurones. This excitation of vagal motoneurones was blocked by pretreatment with S-adenosyl-homocysteine (100 μM), an inhibitor of methylation reactions. It is concluded that the inhibitory activity of S-adenosyl-l-methionine on the firing rate of vagal motoneurones is due to its metabolic transformation into adenosine which then acts on adenosine receptors. The excitatory effect on firing rate appears to be due to other actions, possibly including methylation reactions of key components of signal transduction mechanisms.

AB - We used the patch clamp technique applied to an in vitro brain slice preparation to examine the changes in firing activity of single dorsal vagal motoneurones exposed to S-adenosyl-methionine. In approximately 70% of the neurones tested, S-adenosyl-l-methionine (1-100 μM) decreased the spontaneously occurring firing in a dose dependent manner; the plateau decrease was 40±6%. The peak effect was observed approximately 5 min after the superfision with S-adenosyl-l-methionine was started, and was usually reversible upon wash out of S-adenosyl-l-methionine from the superfusing chamber. No effect of the control salt of S-adenosyl-l-methionine, 1,4-butane-disulfonate·Na (100 μM), was observed. The frequency of discharge observed upon depolarization steps from hyperpolarized potentials was reduced to 34±17% (n=11) of control upon S-adenosyl-l-methionine (100 μM) superfusion; no effect of S-adenosyl-l-methionine was observed on the action potential threshold. Preincubation with adenosine receptor antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 10 nM) and 3,7-dimethyl-1-propargylxanthine (DMPX, 50 μM), reversed the S-adenosyl-l-methionine-induced inhibition of firing rate, and in fact, in the presence of these adenosine antagonists, S-adenosyl-l-methionine increased the firing rate of vagal motoneurones. This excitation of vagal motoneurones was blocked by pretreatment with S-adenosyl-homocysteine (100 μM), an inhibitor of methylation reactions. It is concluded that the inhibitory activity of S-adenosyl-l-methionine on the firing rate of vagal motoneurones is due to its metabolic transformation into adenosine which then acts on adenosine receptors. The excitatory effect on firing rate appears to be due to other actions, possibly including methylation reactions of key components of signal transduction mechanisms.

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