TRP-independent inhibition of the phospholipase C pathway by natural sensory ligands.
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 PLCdelta1 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.
Kim
Kyung Yoon
KY
Korea University Graduate School of Medicine, Seoul 136-705, Republic of Korea.
Bang
Sangsu
S
Han
Shanshu
S
Nguyen
Yen Hoang
YH
Kang
Tong Mook
TM
Kang
Keon Wook
KW
Hwang
Sun Wook
SW
D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002164:Camphor / Q000494:pharmacology*; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D008024:Ligands; D008610:Menthol / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism; D050053:TRPM Cation Channels / Q000187:drug effects / Q000378:metabolism*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D008024:Ligands; D018048:Receptors, Purinergic P2; D050053:TRPM Cation Channels; D008610:Menthol; D000244:Adenosine Diphosphate; D002164:Camphor; D000171:Acrolein; D010738:Type C Phospholipases; C012843:cinnamaldehyde; D002118:Calcium