TRP channels as drug targets.
Ca2+ channel antagonists acting on electrically-excitable cells have proved to be valuable therapeutic agents. The discovery of such agents and the identification of their molecular target resulted from the investigation of unexpected actions of known pharmacological agents. Ca2+ influx through receptor-operated channels in electrically non-excitable cells such as leukocytes is also functionally important, but to date the channels involved have not been successfully exploited as drug targets for anti-inflammatory therapy. Until recently, research in this area has been hindered by the lack of obvious molecular identity, but the emergence of the transient receptor potential (TRP) cation family has yielded promising candidates which may underpin the different receptor-operated Ca2+ influx pathways present in leukocytes. In addition, receptor-operated Ca2+ influx channels are also expressed in electrically-excitable cells suggesting that receptor-operated Ca2+ entry pathways are likely to be of wider significance and emphasizes the breadth of their potential as novel, and as yet, unexplored and unexploited drug targets.
Li
Su
S
Novartis Respiratory Research Centre, Wimblehurst Road, Horsham, West Sussex, RH12 5AB, UK.
Westwick
John
J
Cox
Brian
B
Poll
Chris T
CT
D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D015220:Calcium Channels / Q000187:drug effects*; D015195:Drug Design; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D050052:TRPC Cation Channels
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D050052:TRPC Cation Channels; D002118:Calcium