LACK OF DIRECT CONNECTION BETWEEN ARACHIDONIC-ACID RELEASE AND PROSTANOID SYNTHESIS UPON DIFFERENTIATION OF U937 CELL

The changes in AA incorporation and release as well as prostanoid synt hesis upon differentiation of human premonocytic cell line, U937, indu ced by three functionally diverse agents-phorbol ester (TPA), dimethyl sulfoxide (DMSO), and retinoic acid (RA) have been investigated. The rate of AA incorporation into the cells remained unchanged whereas a 3 - to B-fold increase in AA release upon stimulation with Ca2+-ionophor e A23187 as compared to undifferentiated cells was observed. While und ifferentiated cells were incapable to metabolise AA via the cyclooxyge nase pathway all three types of differentiated U937 cells produced TxB (2) and PGE(2). Only TPA-differentiated cells responded with a B-fold increase of prostanoid synthesis after A23187 stimulation, whereas in DMSO-differentiated cells prostanoid synthesis was slightly stimulated by A23187 and in RA-differentiated cells it was not stimulated at all . Thus, agonist-induced prostanoid synthesis in differentiated cells i s dependent on the nature of differentiating agent and does not correl ate with AA liberation. (C) 1998 Academic Press.