Endogenous adenosine modulates electrically-evoked ACh secretion via A3 receptors at the mouse neuromuscular junction (NMJ)

MAXIMILIANO HURTADO PASO ; JUAN F GUARRACINO; JAVIER A GONZALEZ SANABRIA; ADRIANA LOSAVIO; TAMARA FRONTERA

Mar del Plata

Congreso; LXIII Reunión Sociedad Argentina de Investigación Clínica; 2018

Sociedad Argentina de Investigación Clínica

At mammalian NMJ, ATP is co-released with ACh, and metabolized via ecto-nucleotidases to adenosine (AD), which modulates ACh release via presynaptic inhibitory A1 and facilitatory A2A receptors (R). We have demonstrated, by pharmacological and immunohistochemical assays, that A3AD R are also present at the motor nerve terminals and that they may be activated by AD and its metabolite inosine (INO). Our aim was to elucidate if A3R are activated by endogenous AD when the nerve is stimulated at 0.5 Hz (50 pulses), 5 Hz (750 pulses) or 50 Hz (750 pulses or 5 bursts of 150 pulses, 20-s interburst interval). In phrenic-diaphragm preparations (CF1 mice), we studied the action of the specific antagonist or agonist for A3R (MRS-1191 5 µM; INO 100 µM) upon EPP amplitude. We found that at 0.5 Hz (n=4) and 5 Hz (n=4), MRS-1191 did not change the amplitudes of the 1º EPP, mean EPPs, last 20 EPPs and last 20 EPPs/1º EPP ratio, while INO (0.5 Hz n=6; 5 Hz n=4) significantly reduced 1º EPP amplitude, mean EPP amplitude and last 20 EPPs. At 0.5 Hz, INO did not alter last 20 EPPs/1º EPP ratio but at 5 Hz this relation was higher than in control (p