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Am J Physiol Gastrointest Liver Physiol 292: G1483-G1489, 2007. First published February 22, 2007; doi:10.1152/ajpgi.00450.2006
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NEUROREGULATION AND MOTILITY

Inhibitory neuromuscular transmission mediated by the P2Y1 purinergic receptor in guinea pig small intestine

Guo-Du Wang, Xi-Yu Wang, Hong-Zhen Hu, Sumei Liu, Na Gao, Xiucai Fang, Yun Xia, and Jackie D. Wood

Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, Ohio

Submitted 29 September 2006 ; accepted in final form 8 February 2007

ATP 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 P2Y1 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 P2Y1 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{omega}-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 Ca2+-operated K+ 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 5'-triphosphate; neurotransmission; enteric nervous system; intestinal motility; smooth muscle



Address for reprint requests and other correspondence: J. D. Wood, Dept. of Physiology and Cell Biology, The Ohio State Univ., College of Medicine and Public Health, 304 Hamilton Hall, 1645 Neil Ave., Columbus, OH 43210 (e-mail: wood.13{at}osu.edu)




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