Understanding the mechanisms underlying contraction and relaxation of airway smooth muscle (ASM) is crucial to furthering our knowledge of the processes governing bronchoconstriction and bronchodilatation, and may additionally throw light upon the pathogenesis of conditions such as asthma where bronchial reactivity is altered. Recent advances in the field of cellular signal transduction mechanisms in general, and in inositol phosphate metabolism in particular, have resulted in a clearer understanding of the molecular basis of pharmacomechanical coupling in ASM and a consequent growth of interest in this area of research . This review deals specifically with the relevance of the inositol phospholipid system to the function of ASM . It should be remembered that this pathway has been shown to be an important means of signal transduction in a wide variety of other cell types found in the lung, and is likely to be involved in many responses in the airways .
Sources of activator calcium
The contractile response of ASM to a variety of spasmogens including histamine, 5-hydroxy tryptamine, and acetylcholine is dependent upon a rise in intracellular free Cat + .1 There are two possible sources of Ca 2+ to account for the observed rise ; external Cat+, which can enter the cell through voltage dependent or voltage independent (receptor-operated) channels, and internal Cat+, which can be released from stores within the sarcoplasmic reticulum. Although ASM contraction can be induced by concentrations of KCI or tetraethylammonium high enough to cause membrane depolarisation with consequent Cat+ influx through voltage dependent channels 2,3 an effect which can be blocked by dihydropyridines, 4 the spasmogenic effect of acetylcholine is independent of