Pharmacological modulation of diacylglycerol-sensitive TRPC3/6/7 channels

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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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