1.
TRP channels as drug targets.
Li, S, Westwick, J, Cox, B, Poll, CT
Novartis Foundation symposium. 2004;:204-13; discussion 213-21, 263-6
Abstract
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.
2.
Transient receptor potential (TRP) channels as potential drug targets in respiratory disease.
Li, S, Westwick, J, Poll, C
Cell calcium. 2003;(5-6):551-8
Abstract
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).