Open AccessSecond messengers, ion channels and pharmacology of airway smooth muscle
Author(s) -
Hall I.P.
Publication year - 2000
Publication title -
european respiratory journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.021
H-Index - 241
eISSN - 1399-3003
pISSN - 0903-1936
DOI - 10.1034/j.1399-3003.2000.01523.x
Subject(s) - second messenger system , microbiology and biotechnology , adenylyl cyclase , signal transduction , cyclic adenosine monophosphate , intracellular , ion channel , phospholipase c , vascular smooth muscle , chemistry , biology , receptor , endocrinology , medicine , smooth muscle
The airway smooth muscle cell is the chief effector cell governing the control of airway calibre in the human lung. The contractile state of the airway smooth muscle cell is predominantly influenced by the balance of constrictor and relaxant stimuli. Agents such as histamine and acetylcholine cause airway smooth muscle cells to contract through activation of specific cell surface receptors and engagement of signal transduction pathways and/or ion channels. The predominant pathway mediating constriction is activation of phospholipase C, with release of inositol 1,4,5‐triphosphate and elevation of intracellular calcium levels. Relaxation is brought about predominantly by stimulation of adenylyl cyclase‐coupled receptors ( e.g. the β 2 ‐adrenoceptor) resulting in elevation of cell cyclic adenosine monophosphate content. Complex crosstalk occurs between both of these pathways and also ion channels expressed on the airway smooth muscle cell membrane, leading to careful regulation of airway smooth muscle tone. A greater understanding of the mechanisms governing control of these pathways will lead to the identification of novel therapeutic targets which will in turn lead to new agents for the treatment of asthma.