Regulation of eicosanoid synthesis by whole fetal rat brain ex vivo

Intact cerebral hemispheres from 20-d-old rat fetuses incubated at 37 degrees C in Dulbecco's Modified Eagle Medium (DMEM) synthesize and release a number of arachidonic acid derived metabolites, such as thromboxane B2 (TxB2), 6-keto prostaglandin F1 alpha (6k-PGF1 alpha), and prostaglandin E2 (PGE2) eicosanoids. Synthesis is time-dependent and is stimulated upon addition of the calcium ionophore A23187 (10 microM). Ionophore stimulation is prevented by EDTA/EGTA (5 mM each) ion chelators, dextran-70 (5%), and indomethacin (10 microM), a potent cyclooxygenase inhibitor. Ca2+ (2 mM) enhances ionophore-mediated formation of TxB2, 6K-PGF1 alpha, and PGE2 by 2.5-, 2.9-, and 4.2-fold, respectively; Mg2+ blocks ionophore stimulation. Freezing and thawing enhances release of eicosanoids to a level nearly the same as that obtained in the presence of A23187, indicating a common mode of action.