Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1994-1-27
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++.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
267
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1205-14
pubmed:dateRevised
2007-11-15
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
pubmed:year
1993
pubmed:articleTitle
Distinct muscarinic receptors, G proteins and phospholipases in esophageal and lower esophageal sphincter circular muscle.
pubmed:affiliation
Department of Medicine, Rhode Island Hospital, Providence.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.