Excitation-contraction coupling mechanisms in airway smooth muscle: new targets in drug design.
Homeostatic regulation of Ca2+ levels within airway smooth muscle cells, and the consequences of changes in intracellular Ca2+ levels are reviewed, and a number of mechanisms are identified as targets for drug action. In the prophylaxis of asthma--by preventing the induction of contraction--the opportunities relate to receptor antagonism, the inhibition of Ca2+ influx, the inhibition of intracellular Ca2+ release, calmodulin antagonism, and the antagonism of contractile proteins. In the symptomatic relief of asthma--by reversal of established contractile responses--the opportunities relate to the inhibition of Ca2+ influx, the inhibition of inositol trisphosphate metabolism, the inhibition of protein kinase C, and the augmentation of Ca2+ removal mechanisms.
Rodger
I W
IW
Department of Physiology & Pharmacology, Royal College, University of Strathclyde, Glasgow, Scotland.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015195:Drug Design; D006801:Humans; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects
D002118:Calcium