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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1994-1-27
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pubmed:abstractText |
Acetylcholine (ACh)-induced contraction of esophageal circular smooth muscle cells was inhibited by the M2 muscarinic antagonist methoctramine. In lower esophageal sphincter (LES) cells contraction was inhibited by the M3 antagonist p-fluoro-hexa-hydro-sila-difenidol (pF-HSD). Pertussis toxin (PTX) reduced ACh-induced contraction of esophageal but not of LES cells, which suggested that different receptor-linked G proteins are involved. Antibodies against G13 antagonized contraction of esophageal cells and G9-G11 antibodies antagonized contraction of LES cells. The phosphatidylinositol-specific phospholipase C (PLC) inhibitors, U-73122 and neomycin, reduced ACh-induced contraction of LES but not of esophageal cells. Conversely, propranolol and p-chloromercuribenzoic acid (pCMB), which inhibit a phosphatidylcholine-specific phospholipase D (PLD)-dependent pathway, reduced contraction of esophageal but not of LES muscle cells. At 1 and 5 sec after the administration of ACh (10(-5) M), inositol 1,4,5-trisphosphate (IP3) increased only in LES muscle, which suggested that contraction results from PLC-induced IP3 production in the LES but not in the esophagus. The IP3 receptor antagonist heparin, and depletion of intracellular Ca++ stores by thapsigargin or A23187, inhibited ACh-induced contraction of LES but not of esophageal muscle. It was concluded that ACh-induced esophageal contraction depends preferentially on M2 receptors, a PTX-sensitive G13 protein, phosphatidylcholine-specific PLD and production of diacylglycerol (DAG) and is independent of IP3 formation and the release of intracellular Ca++. Conversely, LES contraction is mediated through M3 receptors, a PTX-insensitive G9-G11 protein, activation of PLC, IP3 formation and the release of intracellular Ca++.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcholine,
http://linkedlifedata.com/resource/pubmed/chemical/Diglycerides,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase D,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Muscarinic,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
267
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1205-14
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:8263781-Acetylcholine,
pubmed-meshheading:8263781-Animals,
pubmed-meshheading:8263781-Cats,
pubmed-meshheading:8263781-Diglycerides,
pubmed-meshheading:8263781-Enzyme Activation,
pubmed-meshheading:8263781-Esophagogastric Junction,
pubmed-meshheading:8263781-Esophagus,
pubmed-meshheading:8263781-Female,
pubmed-meshheading:8263781-GTP-Binding Proteins,
pubmed-meshheading:8263781-Inositol 1,4,5-Trisphosphate,
pubmed-meshheading:8263781-Male,
pubmed-meshheading:8263781-Muscle, Smooth,
pubmed-meshheading:8263781-Muscle Contraction,
pubmed-meshheading:8263781-Pertussis Toxin,
pubmed-meshheading:8263781-Phosphatidylinositols,
pubmed-meshheading:8263781-Phospholipase D,
pubmed-meshheading:8263781-Phospholipases,
pubmed-meshheading:8263781-Receptors, Muscarinic,
pubmed-meshheading:8263781-Sensitivity and Specificity,
pubmed-meshheading:8263781-Signal Transduction,
pubmed-meshheading:8263781-Type C Phospholipases,
pubmed-meshheading:8263781-Virulence Factors, Bordetella
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pubmed:year |
1993
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pubmed:articleTitle |
Distinct muscarinic receptors, G proteins and phospholipases in esophageal and lower esophageal sphincter circular muscle.
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pubmed:affiliation |
Department of Medicine, Rhode Island Hospital, Providence.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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