| Molecular mechanisms of cross-inhibition between nicotinic acetylcholine receptors and P2X receptors in myenteric neurons and HEK-293 cells. | |
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MedLine Citation:
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PMID: 20426799 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: P2X(2) and nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic excitation in the enteric nervous system. P2X receptors and nAChRs are functionally linked. This study examined the mechanisms responsible for interactions between P2X2 and alpha3beta4subunit-containing nAChRs. METHODS: The function of P2X2 and alpha3beta4 nAChRs expressed by HEK-293 cells and guinea pig ileum myenteric neurons in culture was studied using whole-cell patch clamp techniques. KEY RESULTS: In HEK-293 cells expressing alpha3beta4 nAChRs and P2X2 receptors, co-application of ATP and acetylcholine caused inward currents that were 56 +/- 7% of the current that should occur if these channels functioned independently (P < 0.05, n = 9); we call this interaction cross-inhibition. Cross-inhibition did not occur in HEK-293 cells expressing alpha3beta4 nAChRs and a C-terminal tail truncated P2X2 receptor (P2X2TR) (P > 0.05, n = 8). Intracellular application of the C-terminal tail of the P2X2 receptor blocked nAChR-P2X receptor cross-inhibition in HEK-293 cells and myenteric neurons. In the absence of ATP, P2X2 receptors constitutively inhibited nAChR currents in HEK-293 cells expressing both receptors. Constitutive inhibition did not occur in HEK-293 cells expressing alpha3beta4 nAChRs transfected with P2X2TR. Currents caused by low (< or =30 micromol L(-1)), but not high (> =100 micromol L(-1)) concentrations of ATP in cells expressing P2X2 receptors were inhibited by co-expression with alpha3beta4 nAChRs. CONCLUSIONS & INFERENCES: The C-terminal tail of P2X2 receptors mediates cross-inhibition between alpha3beta4 nAChR-P2X2 receptors. The closed state of P2X2 receptors and nAChRs can also cause cross-inhibition. These interactions may modulate transmission at enteric synapses that use ATP and acetylcholine as co-transmitters. |
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Authors:
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D A Decker; J J Galligan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-04-23 |
Journal Detail:
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Title: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Volume: 22 ISSN: 1365-2982 ISO Abbreviation: Neurogastroenterol. Motil. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-28 Completed Date: 2010-11-22 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 9432572 Medline TA: Neurogastroenterol Motil Country: England |
Other Details:
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Languages: eng Pagination: 901-8, e235 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Michigan State University, East Lansing, MI, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholine
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metabolism Adenosine Triphosphate / metabolism Animals Cell Line Cholinergic Agents / metabolism Enteric Nervous System / physiology Guinea Pigs Humans Myenteric Plexus / cytology* Neurons / cytology, physiology* Nicotinic Antagonists / metabolism* Patch-Clamp Techniques Receptors, Nicotinic / metabolism* Receptors, Purinergic P2X2 / antagonists & inhibitors*, metabolism Synaptic Transmission / physiology |
| Grant Support | |
ID/Acronym/Agency:
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DK57039/DK/NIDDK NIH HHS; R01 DK057039-09/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cholinergic Agents; 0/Nicotinic Antagonists; 0/Receptors, Nicotinic; 0/Receptors, Purinergic P2X2; 0/nicotinic receptor alpha3beta4; 51-84-3/Acetylcholine; 56-65-5/Adenosine Triphosphate |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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