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Significant recent discoveries have shown that the P2Y1 purinergic receptor subtype is expressed in the enteric nervous system and at intestinal neuromuscular junctions. Secretomotor neurons, which release vasoactive intestinal peptide at their junctions with intestinal secretory glands, express the P2Y1 receptor. Synaptically released ATP acts at these P2Y1 receptors to stimulate glandular secretion of electrolytes and H2O. Motor neurons in the enteric nervous system release ATP as an inhibitory neurotransmitter at neuromuscular junctions in the intestinal circular muscle coat; this action of ATP is mediated by the P2Y1 receptor. The emerging evidence for significant involvement of P2Y1 receptors in local enteric neural control and coordination of intestinal secretion and motility suggests that either the receptors themselves or steps in the post-P2Y1 receptor signal transduction cascade might be potential therapeutic targets.