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| Item Type: | Review |
|---|---|
| Title: | Pharmacological modulation of diacylglycerol-sensitive TRPC3/6/7 channels |
| Creators Name: | Harteneck, C. and Gollasch, M. |
| Abstract: | Members of the classic type of transient receptor potential channels (TRPC) represent important molecules involved in hormonal signal transduction. TRPC3/6/7 channels are of particular interest as they are components of phospholipase C driven signalling pathways. Upon receptor-activation, G-protein-mediated stimulation of phospholipase C results in breakdown of phosphatidylinositides leading to increased intracellular diacylglycerol and inositol-trisphosphate levels. Diacylglycerol activates protein kinase C, but more interestingly diacylglycerol directly activates TRPC2/3/6/7 channels. Molecular cloning, expression and characterization of TRP channels enabled reassignment of traditional inhibitors of receptor-dependent calcium entry such as SKF-96365 and 2-APB as blockers of TRPC3/6/7 and several members of non-classic TRP channels. Furthermore, several enzyme inhibitors have also been identified as TRP channel blockers, such as ACA, a phospholipase A(2) inhibitor, and W-7, a calmodulin antagonist. Finally, the naturally occurring secondary plant compound hyperforin has been identified as TRPC6-selective drug, providing an exciting proof of concept that it is possible to generate TRPC-selective channel modulators. The description of Pyr3 as the first TRPC3-selective inhibitor shows that not only nature but also man is able to generate TRP-selective modulators. The review summarizes the data on pharmacological modification of TRPC3/6/7. Sheds lights on the current knowledge and historical development of pharmacological modulators of TRPC3/6/7. Our analysis indicates that Pyr3 and hyperforin provide promising core structures for the development of new, skeletive and more potent modulators of TRPC3/6/7 activity. |
| Keywords: | Diacylglycerol, Hyperforin, ACA, SFKF-96365, Calcium Homeostasis, Animals |
| Source: | Current Pharmaceutical Biotechnology |
| ISSN: | 1389-2010 |
| Publisher: | Bentham |
| Volume: | 12 |
| Number: | 1 |
| Page Range: | 35-41 |
| Date: | 1 January 2011 |
| Official Publication: | https://doi.org/10.2174/138920111793937943 |
| PubMed: | View item in PubMed |
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