Inhibitory neuromuscular transmission mediated by the P2Y1 purinergic receptor in guinea pig small intestine.
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 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(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 Ca(2+)-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 P2Y(1) purinergic receptor subtype mediates the action of ATP.
Wang
Guo-Du
GD
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, USA.
Wang
Xi-Yu
XY
Hu
Hong-Zhen
HZ
Liu
Sumei
S
Gao
Na
N
Fang
Xiucai
X
Xia
Yun
Y
Wood
Jackie D
JD
D000200:Action Potentials; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005769:Gastrointestinal Motility; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D009197:Myenteric Plexus / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D004791:Enzyme Inhibitors; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D026902:Potassium Channel Blockers; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D009569:Nitric Oxide; D013779:Tetrodotoxin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester