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Adenosine A 1 and A 2A receptor‐mediated modulation of acetylcholine release in the mice neuromuscular junction
Author(s) -
Garcia Neus,
Priego Mercedes,
Obis Teresa,
Santafe Manel M.,
Tomàs Marta,
Besalduch Nuria,
Lanuza MªAngel,
Tomàs Josep
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12220
Subject(s) - adenosine , acetylcholine , neuromuscular transmission , neuromuscular junction , neurotransmission , adenosine a1 receptor , chemistry , agonist , endocrinology , neuroscience , medicine , cgs 21680 , receptor , adenosine receptor , biology , biochemistry
Abstract Immunocytochemistry shows that purinergic receptors (P1Rs) type A1 and A2A (A 1 R and A 2 A R , respectively) are present in the nerve endings at the P6 and P30 Levator auris longus ( LAL ) mouse neuromuscular junctions ( NMJ s). As described elsewhere, 25 μ m adenosine reduces (50%) acetylcholine release in high Mg 2+ or d ‐tubocurarine paralysed muscle. We hypothesize that in more preserved neurotransmission machinery conditions (blocking the voltage‐dependent sodium channel of the muscle cells with μ‐conotoxin GIIIB ) the physiological role of the P1Rs in the NMJ must be better observed. We found that the presence of a non‐selective P1R agonist (adenosine) or antagonist (8‐ SPT ) or selective modulators of A 1 R or A 2 A R subtypes ( CCPA and DPCPX , or CGS ‐21680 and SCH ‐58261, respectively) does not result in any changes in the evoked release. However, P1Rs seem to be involved in spontaneous release (miniature endplate potentials MEPP s) because MEPP frequency is increased by non‐selective block but decreased by non‐selective stimulation, with A 1 Rs playing the main role. We assayed the role of P1Rs in presynaptic short‐term plasticity during imposed synaptic activity (40 Hz for 2 min of supramaximal stimuli). Depression is reduced by micromolar adenosine but increased by blocking P1Rs with 8‐ SPT . Synaptic depression is not affected by the presence of selective A 1 R and A 2 A R modulators, which suggests that both receptors need to collaborate. Thus, A 1 R and A 2 A R might have no real effect on neuromuscular transmission in resting conditions. However, these receptors can conserve resources by limiting spontaneous quantal leak of acetylcholine and may protect synaptic function by reducing the magnitude of depression during repetitive activity.