Facilitation of electrically-evoked ACh secretion when activating A2A adenosine receptors at mammalian neuromuscular junction (NMJ)

JAVIER GONZÁLEZ SANABRIA; ADRIANA LOSAVIO; MAXIMILIANO HURTADO PASO; JUAN GUARRACINO; TAMARA FRONTERA

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Congreso; LXII Reunión Sociedad Argentina de Investigación Clínica; 2017

Sociedad Argentina de Investigación Clínica

At mammalian NMJ, ATP is co-released with ACh, and metabolizedvia ecto-nucleotidases to adenosine (AD), which modulatesACh release through presynaptic inhibitory A1 or facilitatory A2Areceptors (R). We have found that during high stimulation frequency(50 Hz) enough AD is generated, able to reduce neurosecretion viaA1R whereas A2AR were not activated. To analyze if more endogenousAD is required to activate A2AR, the action of specific A2Aantagonist or agonist (SCH-58261 [SCH, 50 nM] or PSB-0777 [PSB,20 nM]) was evaluated in phrenic-diaphragm preparations (CF1mice) when the nerve was stimulated at 100 Hz. Considering that, atfrequencies lower than 100 Hz, A2AR are not occupied by AD andthat, at high [K+]o, L-type voltage-gated calcium channels (L-VGCCs)are involved in the mechanism of facilitation, we studied the effect ofPSB in the presence of the L-VGCC blocker nitrendipine (NIT, 5 μm)at 0.5 Hz, 5 Hz and 50 Hz (750 pulses each). At 100 Hz, SCH (n= 4)did not change the amplitude of the 1º EPP but reduced mean EPPamplitude (p