Evidence for constitutively-active adenosine receptors at mammalian motor nerve endings

Timothy J Searl*, Eugene M Silinsky

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

A study was made to determine if constitutively active adenosine receptors are present at mouse motor nerve endings. In preparations blocked by low Ca 2+/high Mg 2+ solution, 8-cyclopentyl-1,3,dipropylxanthine (CPX, 10-100 nM), which has been reported to be both an A 1 adenosine receptor antagonist and inverse agonist, produced a dose-dependent increase in the number of acetylcholine quanta released by a nerve impulse. Adenosine deaminase, which degrades ambient adenosine into its inactive congener, inosine, failed to alter the response to 100 nM CPX. 8-Cyclopentyltheophylline (CPT, 3 μM), a competitive inhibitor at A 1 adenosine receptors, prevented the increase in acetylcholine release produced by CPX. At normal levels of acetylcholine release, neither adenosine deaminase nor CPX affected acetylcholine release at low frequencies of nerve stimulation in (+)-tubocurarine blocked preparations. The results suggest that a proportion of the acetylcholine release process is controlled by constitutively active adenosine receptors at murine motor nerve endings, providing the first evidence for constitutive activity of G-protein-coupled receptors that modulate the function of mammalian nerve endings.

Original languageEnglish (US)
Pages (from-to)38-41
Number of pages4
JournalEuropean Journal of Pharmacology
Volume685
Issue number1-3
DOIs
StatePublished - Jun 15 2012

Fingerprint

Purinergic P1 Receptors
Nerve Endings
Acetylcholine
Adenosine Deaminase
Purinergic P1 Receptor Antagonists
Tubocurarine
Inosine
G-Protein-Coupled Receptors
Adenosine
Action Potentials

Keywords

  • A adenosine receptor
  • Constitutive activity
  • End-plate potential
  • G-protein coupled receptor
  • Neuromuscular junction
  • Neurotransmitter release

ASJC Scopus subject areas

  • Pharmacology

Cite this

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abstract = "A study was made to determine if constitutively active adenosine receptors are present at mouse motor nerve endings. In preparations blocked by low Ca 2+/high Mg 2+ solution, 8-cyclopentyl-1,3,dipropylxanthine (CPX, 10-100 nM), which has been reported to be both an A 1 adenosine receptor antagonist and inverse agonist, produced a dose-dependent increase in the number of acetylcholine quanta released by a nerve impulse. Adenosine deaminase, which degrades ambient adenosine into its inactive congener, inosine, failed to alter the response to 100 nM CPX. 8-Cyclopentyltheophylline (CPT, 3 μM), a competitive inhibitor at A 1 adenosine receptors, prevented the increase in acetylcholine release produced by CPX. At normal levels of acetylcholine release, neither adenosine deaminase nor CPX affected acetylcholine release at low frequencies of nerve stimulation in (+)-tubocurarine blocked preparations. The results suggest that a proportion of the acetylcholine release process is controlled by constitutively active adenosine receptors at murine motor nerve endings, providing the first evidence for constitutive activity of G-protein-coupled receptors that modulate the function of mammalian nerve endings.",
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