Effect of endogenous purines on electrically evoked ACh release at the mouse neuromuscular junction

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

JOURNAL OF NEUROSCIENCE RESEARCH

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2022 p. 1933 - 1950

0360-4012

At the mouse neuromuscular junction, ATP, which is co-released with the neurotransmitter ACh, and its metabolite adenosine, modulate neurotransmitter release by activating presynaptic inhibitory P2Y13 receptors (a subtype of ATP/ADP receptor), inhibitory A1 and A3 adenosine receptors and excitatory A2A adenosine receptors. To study the effect of endogenous purines, when phrenic-diaphragm preparations are depolarized by different nerve stimulation patterns, we analyzed the effect of the antagonists for P2Y13, A1, A3 and A2A receptors (AR-C69931MX, DPCPX, MRS-1191, and SCH-58261, respectively) on the amplitude of the end-plate potentials (EPPs) of the trains, and contrasted these results with those obtained with the selective agonists of these receptors (2-MeSADP, CCPA, inosine and PSB-0777, respectively). During continuous 0.5-Hz stimulation, the amount of endogenous purines was not enough to activate purinergic receptors, while at continuous 5 Hz-stimulation, an incipient action of endogenous purines on P2Y13, A1 and A3 receptors might be evident just at the end of the trains. During continuous 50 Hz-stimulation, the concentration of endogenous ATP/ADP and adenosine exerted an inhibitory action on ACh release after of the initial phase of the train, but when the nerve was stimulated at intermittent 50 Hz (5 bursts), this behavior was not observed. Excitatory A2A receptors were only activated when continuous 100 Hz-stimulation was applied. In conclusion, when motor nerve terminals are depolarized by repetitive stimulation of the phrenic nerve, endogenous ATP/ADP and adenosine are able to fine-tune neurosecretion depending on the frequency and pattern of stimulation.