EFFECT OF H-2-RECEPTOR ANTAGONISTS ON INDOMETHACIN-INDUCED LYSOSOMAL-ENZYME RELEASE FROM RAT GASTRIC-MUCOSA

The in vivo effect of indomethacin and three H-2-receptor antagonists - cimetidine, ranitidine, and famotidine - on gastric damage and on th e activity of lysosomal enzymes and on proteins was examined in rat ga stric mucosa and serum. The activities of the lysosomal enzymes N-acet yl-beta-glucosaminidase (NAGA), acid phosphatase (APh), and beta-D-glu curonidase (GLU) decreased significantly in gastric mucosa 2, 4, 6 and 12 h after subcutaneous administration of indomethacin (20 mg/kg). Th e serum activities of the lysosomal enzymes were unchanged. A decrease of protein in gastric mucosa was observed 4 and 6 h after indomethaci n administration. Pretreatment with cimetidine and ranitidine reduced dose-dependently the length of gastric lesions induced by indomethacin , as well as the decrease in lysosomal enzyme mucosal activities. Famo tidine, in spite of its antiulcer effect, failed to prevent the releas e of NAGA and APh, yet proved to inhibit GLU release. The results sugg est that, in addition to their gastroprotective effect, H-2-receptor a ntagonists may contribute to lysosomal membrane protection in indometh acin-induced gastric injury.