Changes in inositol 1,4,5-trisphosphate mass in agonist-stimulated human neutrophils

Changes in the endogenous synthesis of inositol 1,4,5-trisphosphate (IP₃) mass have been quantitated in human peripheral neutrophils stimulated with FMLP, LTB₄ and PAF using a recently described, highly specific radioreceptor assay. Each agonist induced a concentration-dependent synthesis of IP₃ which was detectable within 10 seconds after stimulation. IP₃ production was short-lived, returning to basal levels within 90 seconds. The maximal stimulated level of IP₃ in response to FMLP and LTB₄ was 30–50 pmoles/10⁷ neutrophils. PAF was more effective (100 pmoles IP₃/10⁷ neutrophils). The response to FMLP was inhibited by pertussis toxin, but was unaffected by cholera toxin. Pretreatment with cytochalasin B did not enhance IP₃ synthesis. These findings are generally consistent with previous studies employing [³H]myo-inositol-prelabeled cells, and provide one of the first measurements of IP₃ synthesis by mass in agonist-stimulated human neutrophils.