EICOSANOID AND INOSITOL PHOSPHATE RESPONSE TO PLATELET-ACTIVATING-FACTOR (PAF) AND TO A PAF ANTAGONIST IN RAT ASTROGLIAL CELLS

The effects of different concentrations of exogenous platelet-activati ng factor (PAF) on the formation of arachidonic acid-cycloxygenase met abolites and on the production of inositol phosphates have been invest igated in a primary culture of rat astroglial cells. The cells were us ed at confluence and the purity was checked by immunostaining of the c ulture with specific antibodies against glial fibrillary acidic protei n. Incubation of the cells with PAF (range 10(-9) to 10(-6) M) resulte d in maximal accumulation of total inositol phosphate (620 +/- 60% inc rement over basal values, P < 0.001) at the concentration of 10(-8) M, after 1 min of stimulation. Smaller inositol phosphate accumulation o ccurred-at higher concentrations of the agonist and at longer stimulat ion time. After 1 min of stimulation with PAF, the accumulation of the cycloxygenase metabolites, thromboxane B-2 (630 +/- 58 vs 20 +/- 2 pg /mg protein in non-stimulated samples) and 6-keto-prostaglandin F-1 al pha (132 +/- 15 vs 55 +/- 7 pg/mg protein in non-stimulated samples) w as also maximal at 10(-8) M concentration of the agonist. When the cul tures were stimulated with PAF or Ca2+-ionophore after preincubation w ith equimolar concentration of the PAF inhibitor BN 52021, a significa nt inhibition in the synthesis of both inositol phosphates and cycloxy genase metabolites occurred only in the PAF-stimulated cells.