Inositol phosphate turnover in human airways: effect of arachidonic acid metabolism.

The aim of this study was to examine the role of the phospholipase A2-arachidonic acid (PLA2-AA) pathway in response to histamine and the possible effect of AA metabolites on the generation of inositol-phosphates (IPs) in airway smooth muscle cells (SMC). Radiolabelled IPs-were analyzed by high-performance liquid chromatography (HPLC). Indomethacin, a cyclooxygenase inhibitor, potentiated the IP production evoked by a 5-sec application of histamine, while it decreased the effect of a 5-min incubation with the agonist, suggesting a time-dependent modulation of phospholipase C (PLC) activity by prostaglandins (PGs). Exogenous AA elicited the generation of IPs; this effect was suppressed by cyclooxygenase inhibition. Therefore, several steps in the AA metabolic pathways appear to modulate the production of IPs in human airway SMC.