Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Menthol and many of its derivatives produce profound sensory and mental effects. The receptor for menthol has been cloned and named cold- and menthol-sensitive receptor-1 (CMR1) or transient receptor potential channel M8 (TRPM8) receptor. Using a dorsal root ganglion (DRG) and dorsal horn (DH) coculture system as a model for the first sensory synapse in the CNS, we studied menthol effects on sensory synaptic transmission and the underlying mechanisms. We found that menthol increased the frequency of miniature EPSCs (mEPSCs). The effects persisted under an extracellular Ca2+-free condition but were abolished by intracellular BAPTA and pretreatment with thapsigargin. Menthol-induced increases of mEPSC frequency were blocked by 2-aminoethoxydiphenylborane (2-APB) but not affected by the phospholipase C inhibitor U73122 [GenBank] or by the cADP receptor inhibitor 8-bromo-cADPR (8Br-cADPR). Double-patch recordings from DRG-DH pairs showed that menthol could potentiate evoked EPSCs (eEPSCs) and change the paired-pulse ratio of eEPSCs. A Ca2+ imaging study on DRG neurons demonstrated that menthol could directly release Ca2+ from intracellular Ca2+ stores. Menthol-induced Ca2+ release was abolished by 2-APB but not affected by U73122 [GenBank] or 8Br-cADPR. Taken together, our results indicate that menthol can act directly on presynaptic Ca2+ stores of sensory neurons to release Ca2+, resulting in a facilitation of glutamate release and a modulation of neuronal transmission at sensory synapses. Expression of TRPM8 receptor on presynaptic Ca2+ stores, a novel localization for this ligand-gated ion channel, is also strongly suggested.
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PMID:Menthol-induced Ca2+ release from presynaptic Ca2+ stores potentiates sensory synaptic transmission. 1473 62

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.
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PMID:TRP-independent inhibition of the phospholipase C pathway by natural sensory ligands. 1837 3