Significant recent discoveries have shown that the P2Y(1) 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 P2Y(1) receptor. Synaptically released ATP acts at these P2Y(1) receptors to stimulate glandular secretion of electrolytes and H(2)O. 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 P2Y(1) receptor. The emerging evidence for significant involvement of P2Y(1) receptors in local enteric neural control and coordination of intestinal secretion and motility suggests that either the receptors themselves or steps in the post-P2Y(1) receptor signal transduction cascade might be potential therapeutic targets.