Transient receptor potential and other ion channels as pharmaceutical targets in airway smooth muscle cells

被引:12
作者
Ong, HL [1 ]
Barritt, GJ [1 ]
机构
[1] Flinders Univ S Australia, Sch Med, Dept Biochem Med, Adelaide, SA 5001, Australia
关键词
airway smooth muscle; asthma; ion channels; transient receptor potential proteins;
D O I
10.1111/j.1440-1843.2004.00651.x
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Regardless of the triggering stimulus in asthma, contraction of the airway smooth muscle (ASM) is considered to be an important pathway leading to the manifestation of asthmatic symptoms. Therefore, the various ion channels that modulate ASM contraction and relaxation are particularly attractive targets for therapy Although voltage-operated Ca2+ channels (VOCC) are the most extensively characterised Ca2+-permeable channels in ASM cells and are obvious pharmacological targets, blockers of VOCC have not been successful in alleviating ASM contraction in asthma. Similarly, although the Cl- and K+ channels also modulate ASM contraction and relaxation by regulating plasma membrane potential, pharmacological interventions directed against these channels have failed to abrogate ASM contraction in asthma. A large body of evidence suggests that store-operated Ca2+ channels (SOCC) and Ca2+-permeable second messenger- activated non-selective cation channels (NSCC) predominantly mediate ASM contraction. However, development of pharmacological interventions involving these channels has been hampered by the paucity of information regarding their molecular identity. Members of the mammalian transient receptor potential (TRP) protein family, which form voltage- independent channels with variable Ca2+ selectivity that are activated by store depletion and/or by intracellular messengers, are potential molecular candidates for SOCC and NSCC in ASM cells. While the function of TRP channels in ASM cells remains to be elucidated and there are, at present, essentially no good TRP channel antagonists, this group of proteins is a potentially valuable pharmaceutical target for the treatment of asthma.
引用
收藏
页码:448 / 457
页数:10
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