CHARACTERIZATION OF PROSTAGLANDIN-E2 RECEPTORS EXPRESSED ON HUMAN MONOCYTIC LEUKEMIC-CELL LINE, U937

Prostaglandin E2 (PGE2) receptors of a human monocytic leukaemic cell line, U937 cells, have been identified. [H-3]PGE2 binding to these cel ls was found to be saturable and highly specific. Scatchard analysis o f binding data revealed a non-linear plot indicating the presence of t wo independent classes of binding sites with different affinities and capacities. The high-affinity class had K(d1) = 3.1 nM and binding cap acities n1 = 0.6 fmol/10(6) cells, whereas the low-affinity class had K(d2) = 137 nM and capacities n2 = 16 fmol/10(6) cells. Incubation of U937 cells with 3 muM PGE2 stimulated a 15-fold increase in cAMP forma tion compared to basal levels. Prior exposure of these cells with 10 m uM PGE2 for 60 min induced both homologous and heterologous desensitiz ation of adenylate cyclase activity. PGE2 (3 muM) or histamine (100 mu M) showed reduced stimulation of cAMP formation in these desensitized cells compared to controls. The desensitized cells also showed 80% red uction of specific PGE2 binding compared to control cells. Our data su ggest that U937 cells have PGE2 receptors which are linked to the aden ylate cyclase system.