is a putative inhibitory neurotransmitter responsible for inhibitory junction potentials (IJPs) at neuromuscular junctions (IJPs) in the intestine. This study tested the hypothesis that the purinergic P2Y 1 receptor subtype mediates the IJPs. IJPs were evoked by focal electrical stimulation in the myenteric plexus and recorded with "sharp" intracellular microelectrodes in the circular muscle coat. Stimulation evoked three categories of IJPs: 1) purely purinergic IJPs, 2) partially purinergic IJPs, and 3) nonpurinergic IJPs. Purely purinergic IJPs were suppressed by the selective P2Y 1 purinergic receptor antagonist MRS2179. Purely purinergic IJPs comprised 26% of the IJPs. Partially purinergic IJPs (72% of the IJPs) consisted of a component that was abolished by MRS2179 and a second unaffected component. The MRS2179-insensitive component was suppressed or abolished by inhibition of formation of nitric oxide by N -nitro-L-arginine methyl ester (L-NAME) in some, but not all, IJPs. An unidentified neurotransmitter, different from nitric oxide, mediated the second component in these cases. Nonpurinergic IJPs were a small third category (4%) of IJPs that were abolished by L-NAME and unaffected by MRS2179. Exogenous application of ATP evoked IJP-like hyperpolarizing responses, which were blocked by MRS2179. Application of apamin, which suppresses opening of small-conductance Ca 2ϩ -operated K ϩ channels in the muscle, decreased the amplitude of the purinergic IJPs and the amplitude of IJP-like responses to ATP. The results support ATP as a neurotransmitter for IJPs in the intestine and are consistent with the hypothesis that the P2Y1 purinergic receptor subtype mediates the action of ATP. adenosine 5Ј-triphosphate; neurotransmission; enteric nervous system; intestinal motility; smooth muscle INHIBITION OF THE CIRCULAR MUSCULATURE ahead of the advancing bolus is an essential component of peristaltic propulsion in the small and large intestine. This component of the organization of propulsive motility is organized by the enteric nervous system (ENS) and reflects elevated activity in the inhibitory motor innervation of the musculature. Evidence in 1963 first implicated ATP as one of the inhibitory neurotransmitters at neuromuscular junctions in the intestine (9, 10). This role for ATP has been confirmed repeatedly in subsequent years (10,11,12).Inhibitory junction potentials (IJPs) were first reported for the guinea pig taenia coli by Burnstock et al. (9) in 1963 and analyzed in more detail in 1966 (4). Excitation of ENS inhibitory motor neurons by transmural electrical field stimulation or by application of nicotinic receptor agonists is now commonly known to evoke IJPs, which are readily detected with intracellular electrophysiological recording methods, in intestinal circular muscle. In human, guinea pig, dog, and mouse preparations, the IJPs are generally biphasic and consist of an initial large-amplitude and rapidly activating component (fast IJP), followed by a smaller and more slowly activating component (slow IJP...