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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-4-8
pubmed:abstractText
The release of endogenous neurotransmitters plays an important role in the airway mucosal defense system. We studied the in vitro effect of methacholine, a beta-methyl ester of acetylcholine, on the ciliary beat frequency (CBF) of human adenoid explants and its mechanism of action. Tissue explants were cultured at 35 degrees C and covered with 1.0 mL of culture medium: minimum essential Eagle's medium (MEM) containing L-arginine (1.2 x 10(-3) mol/L). Methacholine was added to the cultured tissue at concentrations of 10(-10), 10(-8), and 10(-6) mol/L. The CBF was determined by phase contrast microscopy and microphotometry. Methacholine increased CBF in a dose-dependent manner with a maximum increase of 23.0% +/- 1.8% (p < .001). Atropine (10(-6) mol/L) significantly inhibited the ciliostimulatory effects of methacholine (p < .0007). The role of endogenous prostaglandins in methacholine-induced ciliostimulation was determined by treating specimens with a cyclooxygenase inhibitor (diclofenac sodium). Diclofenac (10(-6) mol/L) significantly inhibited the ciliostimulatory effects of methacholine (p < .0007). To determine if nitric oxide (NO) acts as an intermediary in ciliostimulation by methacholine, endogenous NO production was inhibited by treating specimens with an L-arginine analog, NG-nitro-L-arginine methyl ester (L-NAME), prior to addition of methacholine. L-NAME (10(-6) mol/L) inhibited the effects of methacholine in L-arginine-free MEM (p < .008), and this inhibition was reversed by L-arginine (10(-3) mol/L). To further examine the actions of NO in methacholine-induced ciliostimulation, a cyclic guanosine 3'5'-monophosphate (cGMP) kinase inhibitor (KT-5823) was used, prior to the addition of methacholine. KT-5823 (10(-6) mol/L) significantly inhibited the effects of methacholine (p < .0001). Ciliostimulation by methacholine in human upper airway mucosa involves both prostaglandin and NO second messengers and activation of a cGMP-dependent kinase.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0003-4894
pubmed:author
pubmed:issnType
Print
pubmed:volume
106
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
230-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Signal transduction pathways in modulation of ciliary beat frequency by methacholine.
pubmed:affiliation
Department of Otorhinolaryngology, Mayo Clinic, Rochester, Minnesota 55905, USA.
pubmed:publicationType
Journal Article, In Vitro