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Research ArticleNEUROPHARMACOLOGY

Predominance of Adenosine Excitatory over Inhibitory Effects on Transmission at the Neuromuscular Junction of Infant Rats

Paula A. Pousinha, Alexandra M. Correia, Ana M. Sebastião and Joaquim A. Ribeiro
Journal of Pharmacology and Experimental Therapeutics January 2010, 332 (1) 153-163; DOI: https://doi.org/10.1124/jpet.109.157255
Paula A. Pousinha
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Alexandra M. Correia
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Ana M. Sebastião
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Joaquim A. Ribeiro
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Abstract

Adenosine-induced modulation of neuromuscular transmission in young (3–4-week-old) rats was evaluated. Inhibition of adenosine kinase with iodotubercidin (ITU; 10 μM), which is known to induce adenosine release, enhanced the amplitude of evoked end-plate potentials (EPPs) recorded from innervated diaphragm muscle fibers. This facilitatory effect was transformed into an inhibitory one upon blockade of adenosine A2A receptors with 4-(2-[7-amino-2-(2-furly)[1,2,4]triazolo[2,3-a][1,3,5]triazin5ylamino] ethyl) phenol (ZM 241385) (50 nM); further blockade of adenosine A1 receptors with the selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 10 nM) abolished that inhibition. Adenosine or 2-chloroadenosine (CADO), at submicromolar concentrations, increased the amplitude and the quantal content of EPPs, whereas at low micromolar concentrations they decreased EPP amplitude. Blockade of A1 receptors with DPCPX (10 nM) prevented both excitatory and inhibitory effects, whereas blockade of A2A receptors with ZM241385 (50 nM) prevented only the excitatory effects. DPCPX and ZM241385 also prevented the excitatory effect of the selective A2A receptor agonist 2-[p-(2-carboxyethyl) phenethylamino]-5′-N-ethylcarboxamido adenosine hydrochloride (CGS 21680; 10 nM). CADO (30 nM) also increased neuromuscular transmission in adult (12–16-week-old) rats. It is suggested that at the motor nerve endings, low extracellular concentrations of adenosine activate both A2A and A1 receptors, but activation of A2A receptors predominates over A1 receptors; the activity of A2A receptors might, however, require coactivation of A1 receptors. This facilitatory action of low concentrations of extracellular adenosine upon acetylcholine release may be particularly relevant at developing neuromuscular junctions, where subtle changes in synaptic levels of acetylcholine might influence synaptic stabilization.

Footnotes

  • This work was supported by Fundação do Ministério de Ciência e Tecnologia de Portugal and European Union [Grant NEREPLAS, COST B30]. P.A.P. is the recipient of a Fundação do Ministério de Ciência e Tecnologia de Portugal fellowship [Grant SFRH/BD/28073/2006].

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.109.157255

  • ABBREVIATIONS:

    q.c.
    quantal content
    EPP
    evoked end-plate potential
    NMJ
    neuromuscular junction
    A1R
    adenosine A1 receptor
    A2AR
    adenosine A2A receptor
    AR
    adenosine receptor
    AK
    adenosine kinase
    NMT
    neuromuscular transmission
    AKI
    adenosine kinase inhibitor
    ITU
    5′-iodotubericidin
    CADO
    2-chloroadenosine
    MEPP
    miniature end-plate potential
    ADA
    adenosine deaminase
    DPCPX
    1,3-dipropyl-8-cyclopentylxanthine
    AICAR
    5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside
    ZM 241385
    4-(2-[7-amino-2-(2-furly)[1,2,4]triazolo[2,3-a][1,3,5]triazin5ylamino] ethyl) phenol
    CGS 21680
    2-[p-(2-carboxyethyl) phenethylamino]-5′-N-ethylcarboxamido adenosine hydrochloride
    AMPK
    AMP-activated protein kinase
    ADO
    adenosine.

    • Received June 8, 2009.
    • Accepted September 28, 2009.
  • © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 332 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 332, Issue 1
1 Jan 2010
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Research ArticleNEUROPHARMACOLOGY

Predominance of Adenosine Excitatory over Inhibitory Effects on Transmission at the Neuromuscular Junction of Infant Rats

Paula A. Pousinha, Alexandra M. Correia, Ana M. Sebastião and Joaquim A. Ribeiro
Journal of Pharmacology and Experimental Therapeutics January 1, 2010, 332 (1) 153-163; DOI: https://doi.org/10.1124/jpet.109.157255

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Research ArticleNEUROPHARMACOLOGY

Predominance of Adenosine Excitatory over Inhibitory Effects on Transmission at the Neuromuscular Junction of Infant Rats

Paula A. Pousinha, Alexandra M. Correia, Ana M. Sebastião and Joaquim A. Ribeiro
Journal of Pharmacology and Experimental Therapeutics January 1, 2010, 332 (1) 153-163; DOI: https://doi.org/10.1124/jpet.109.157255
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