期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 628, 期 1-3, 页码 67-74出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2009.11.052
关键词
Capsaicin; Resiniferatoxin; Methyl beta-cyclodextrin; Sphingomyelinase; Ganglioside; N-oleoyldopamine
资金
- NKTH, Science, Please! Research Team on Innovation [SROP-4.2.2/08/1/2008-0011]
- OTKA [T-049027, K-78059]
The transient receptor potential vanilloid 1 (TRPV1) is a noxious heat-sensitive, chemonociceptive cation channel which is expressed in primary sensory neurons of polymodal nociceptors. The present study is devoted to analyse the role of lipid raft constituents in calcium influx evoked by various TRPV1 agonists on sensory neurons and on rTRPV1-transfected CHO cell line. Depletion of cholesterol by methyl P-cyclodextrin (MCD, 1-10 mM) diminished the percent of the calcium uptake response of cultured trigeminal neurons to capsaicin (100 nM) or resiniferatoxin (RTX, 3 nM). In contrast, in TRPV1-transfected cells the inhibition was observed only when capsaicin or N-oleoyldopamine (OLDA, 10 mu M) was applied, but not when RTX, anandamide (AEA, 10 mu M) or pH 5.5 was used for gating. The magnitude of Ca2+-transients evoked by capsaicin (330 nM) was also inhibited in both cell types. Treatment of rTRPV1-expressing cells with sphinomyelinase inhibited the capsaicin-evoked Ca-45-uptake leaving the RTX-induced response unchanged. On the other hand, in trigeminal neurons the effect of both compounds was inhibited by sphingomyelinase treatment. Inhibition of ganglioside biosynthesis by D-threo-1-Phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP, 10-20 mu M) or myriocyn (5-50 nM) diminished similarly capsaicin- or RTX-evoked calcium uptake in both cultured trigeminal neurons and rTRPV1-expressing cells. The present study revealed that depletion of different constituents of lipid raft inhibited gating the TRPV1 cation channel by various vanilloid and non-vanilloid agents. Evidence for a supporting role of cholesterol, sphingomyelin and gangliosides were obtained both in native and TRPV1-transfected cells. Differential modulation of responses to capsaicin and RTX was often observed. (C) 2009 Elsevier B.V. All rights reserved.
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