Transient receptor potential (TRP) channels as potential drug targets in respiratory disease.
Calcium-permeable channels have traditionally been thought of as therapeutic targets in excitable cells. For instance, voltage-operated Ca2+ channels in neurones and smooth muscle cells for neurological and cardiovascular diseases although calcium-permeable channels are also functionally important in electrically non-excitable cells. In the lung, calcium channels play a pivotal role in the activation of all the cell types present, whether resident cells such as airway smooth muscle cells and macrophages or migratory cells such as neutrophils or lymphocytes.Previously, research in this area has been hindered by the lack of obvious molecular identity. More recently, the emergence of the transient receptor potential (TRP) cation family has yielded promising candidates which may underpin the different receptor-operated calcium influx pathways. The challenge now, is to ascribe function to the TRP channels expressed in each cell type as a first step in identifying which TRP channels may be potential drug targets for asthma and chronic obstructive pulmonary disease (COPD) (Fig. 1).
Li
Su
S
Novartis Respiratory Research Centre, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK. su.li@pharma.novartis.com
Westwick
John
J
Poll
Chris
C
D001249:Asthma / Q000188:drug therapy*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000502:physiology*; D015195:Drug Design; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D050052:TRPC Cation Channels
D015220:Calcium Channels; D050052:TRPC Cation Channels; D002118:Calcium