TRP-independent inhibition of the phospholipase C pathway by natural sensory ligands

被引:30
作者
Kim, Kyung Yoon [1 ]
Bang, Sangsu [1 ]
Han, Shanshu [1 ]
Nguyen, Yen Hoang [2 ]
Kang, Tong Mook [2 ]
Kang, Keon Wook [3 ]
Hwang, Sun Wook [1 ]
机构
[1] Korea Univ, Grad Sch Med, Seoul 136705, South Korea
[2] Sungkyunkwan Univ, Dept Physiol, Suwon 440746, South Korea
[3] Chosun Univ, Coll Pharm, Dept Pharmacol, Project Team BK21, Kwangju 501759, South Korea
基金
新加坡国家研究基金会;
关键词
cinnamaldehyde; menthol; camphor; phospholipase C; platelet aggregation;
D O I
10.1016/j.bbrc.2008.03.077
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
Menthol, cinnamaldehyde, and camphor are activators for temperature-sensitive transient receptor potential ion channels (thermoTRPs). Here we found that these three compounds inhibit the phospholipase C (PLC) signaling. P2Y purinoceptor-mediated or histamine receptor-mediated cytosolic calcium mobilization through the PLC pathway was significantly suppressed by menthol, cinnamaldehyde, and camphor. Experiments using a fluorescent pleckstrin homology domain of PLC delta 1 and IP1 accumulation assays demonstrated that direct inhibition of PLC activity occurred upon the addition of the sensory compounds. P2Y receptor-mediated PLC activation is part of the mechanism of platelet aggregation. The three compounds inhibited ADP-induced platelet aggregation. Calcium influx studies showed that thermoTRPs do not function in platelets, suggesting that the anti-aggregation effect is independent of thermoTRP activity. These results suggest that menthol, cinnamaldehyde, and camphor are able to modify PLC signaling and that those effects may lead to changes in cellular functions. This study also identifies new types of compounds that could potentially modulate platelet-related pathological events. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:295 / 300
页数:6
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