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The Journal of pharmacology and experimental therapeutics

Predominance of adenosine excitatory over inhibitory effects on transmission at the neuromuscular junction of infant rats.


PMID 19789361

Abstract

Adenosine-induced modulation of neuromuscular transmission in young (3-4-week-old) rats was evaluated. Inhibition of adenosine kinase with iodotubercidin (ITU; 10 microM), 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 A(2A) 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 A(1) 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 A(1) receptors with DPCPX (10 nM) prevented both excitatory and inhibitory effects, whereas blockade of A(2A) receptors with ZM241385 (50 nM) prevented only the excitatory effects. DPCPX and ZM241385 also prevented the excitatory effect of the selective A(2A) 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 A(2A) and A(1) receptors, but activation of A(2A) receptors predominates over A(1) receptors; the activity of A(2A) receptors might, however, require coactivation of A(1) 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.

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