Linked Life Data

15190109

Source:http://linkedlifedata.com/resource/pubmed/id/15190109

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2004-6-10
pubmed:abstractText
TRPM8 is a nonselective cation channel activated by cold and the cooling compounds menthol and icilin (Peier et al., 2002). Here, we have used electrophysiology and the calcium-sensitive dye Fura-2 to study the effect of pH and interactions between temperature, pH, and the two chemical agonists menthol and icilin on TRPM8 expressed in Chinese hamster ovary cells. Menthol, icilin, and cold all evoked stimulus-dependent [Ca2+]i responses in standard physiological solutions of pH 7.3. Increasing the extracellular [H+] from pH 7.3 to approximately pH 6 abolished responses to icilin and cold stimulation but did not affect responses to menthol. Icilin concentration-response curves were significantly shifted to the right when pH was lowered from 7.3 to 6.9, whereas those with menthol were unaltered in solutions of pH 6.1. When cells were exposed to solutions in the range of pH 8.1-6.5, the temperature threshold for activation was elevated at higher pH and depressed at lower pH. Superfusing cells with a low subactivating concentration of icilin or menthol elevated the threshold for cold activation at pH 7.4, but cooling failed to evoke [Ca2+]i responses at pH 6 in the presence of either agonist. In voltage-clamp experiments in which the intracellular pH was buffered to different levels, acidification reduced the current amplitude of icilin responses and shifted the threshold for cold activation to lower values with half-maximal inhibition at pH 7.2 and pH 7.6. The results demonstrate that the activation of TRPM8 by icilin and cold, but not menthol, is modulated by intracellular pH in the physiological range. Furthermore, our data suggest that activation by icilin and cold involve a different mechanism to activation by menthol.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5364-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
TRPM8 activation by menthol, icilin, and cold is differentially modulated by intracellular pH.
pubmed:affiliation
Novartis Institute for Medical Sciences, London WC1E 6BN, United Kingdom. David.Andersson@pharma.novartis.com
pubmed:publicationType
Journal Article