The production of prostaglandin D2 (PGD2) by rat peritoneal mast cells incubated with N-acetyl glucosamine (GlcNAc) oligomer-specific Datura stramonium agglutinin (DSA) for 10 min in the presence of 0.3 mM Ca2+ was examined. Previously, our group reported that the incubation of rat mast cells with DSA (5 - 100 microg/ml) under similar conditions resulted in a calcium influx and histamine release via a pertussis toxin-sensitive G-protein pathway of the mast cells, and the histamine release was inhibited by haptenic sugar chitooligosaccharides or GlcNAc-specific lectin wheat germ agglutinin (WGA) (K. Matsuda et al., Jpn J Pharmacol 66, 195 - 204 (1994)). DSA (5 - 100 microg/ml) dose-dependently stimulated the mast cells to generate PGD2. Chitooligosaccharides (1% w/v) and WGA (100 microg/ml) inhibited the production of PGD2 induced by 100 microg/ml of DSA, suggesting that the effect of DSA is sugar-specific. A prostaglandin G/H synthase inhibitor NS-398 (N-[cyclohexyloxy-4-nitrophenyl] methanesulfonamide) (10 microM) inhibited the formation of PGD2 induced by DSA (20 microg/ml). These results suggest that the binding of DSA to the corresponding sugar residues on the mast cell surface mediates the signaling of the prostaglandin G/H synthase pathway.