Adenine nucleotides induce presynaptic inhibition of acetylcholine release by activating P2Y 13 receptors at the mouse neuromuscular junction.

JUAN GUARRACINO; ALEJANDRO CINALLI; MARIELA VEGGETTI; VERÓNICA FERNÁNDEZ; LILIANA ROQUEL; ADRIANA LOSAVIO

Córdoba

Congreso; XXVII Congreso Anual Sociedad Argentina de Investigación en Neurociencias; 2012

Sociedad Argentina de Investigación en Neurociencias

At the mouse neuromuscular junction (NMJ), we have demonstrated that ATP reduces ACh release by activating P2Y receptors (R) coupled to Gi/o protein (De Lorenzo et al 2006). Among the 8 P2YR subtypes identified, only P2Y12 and P2Y13 are Gi/o protein-linked and adenine nucleotide-activated receptors. Our aim was to identify the P2YR subtype/s involved in the presynaptic inhibition induced by ATP (phrenic-diaphragm preparations, CF1 mice). We found that the preferential agonist for P2Y12/13R, 2-MeSADP reduced MEPP frequency to 55 % of control values, being more potent in this action than ADP and ATP. This effect was prevented by the selective P2Y12/13R antagonists, 2-MeSAMP and AR-C69931MX. When preparations were incubated with the specific P2Y13R or P2Y12R antagonists (MRS2211 or MRS2395, respectively), we observed that MRS221, but not MRS2395, occluded 2-MeSADP action. Moreover, MRS2211 also abolished the effect of the selective P2Y13R agonist IDP. Similar results were observed when the inhibitory action of 2-MeSADP on EPP amplitude was analyzed in the presence of the antagonists. Immunohistochemical studies confirmed the presence of P2Y13R at the NMJ. These results suggest that at motor nerve terminals, the modulatory effect of ATP/ADP on ACh secretion is mediated by P2Y13R.