Formation of cysteinyl-leukotrienes by human brain tissue

Using sensitive radioimmunoassay techniques, the formation of cysteinyl-leukotrienes (LT) and prostaglandin (PG) F2 alpha was investigated in human brain tissue slices in vitro. Under basal conditions spontaneous release of considerable amounts of LTC4-like material and PGF2 alpha could be detected from slices of both human grey and white matter. Ionophore A23187 stimulated the release of large amounts of LTC4-like material while leaving unaffected the formation of the cyclo-oxygenase product PGF2 alpha. Incubation of grey or white matter in the presence of the cyclo-oxygenase inhibitor indomethacin inhibited the release of PGF2 alpha but did not affect that of LTC4-like material. Preincubation of brain tissue in the presence of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) abolished the ionophore A23187-induced release of LTC4-like material from both grey and white matter and also significantly reduced the spontaneous release of LTC4-like material from white matter slices. Formation of PGF2 alpha was not affected by NDGA. Using the isolated guinea pig ileum the LTC4-like material was shown to possess biological activity which could be antagonized with the slow-reacting substance of anaphylaxis (SRS-A) antagonist FPL 55712. By reversed phase HPLC the immunoreactive LTC4-like material from human grey matter was shown to coelute with authentic LTC4, LTD4 and LTE4, while material from human white matter coeluted with authentic LTD4 and LTE4. The capacity of human brain tissue to synthesize cysteinyl-LT may be important for cellular functions in the central nervous system.