Effect of H2-receptor antagonists on indomethacin-induced lysosomal enzyme release from rat gastric mucosa.

The in vivo effect of indomethacin and three H2-receptor antagonists-cimetidine, ranitidine, and famotidine-on gastric damage and on the activity of lysosomal enzymes and on proteins was examined in rat gastric mucosa and serum. The activities of the lysosomal enzymes N-acetyl-beta-glucosaminidase (NAGA), acid phosphatase (APh), and beta-D-glucuronidase (GLU) decreased significantly in gastric mucosa 2, 4, 6 and 12 h after subcutaneous administration of indomethacin (20 mg/kg). The serum activities of the lysosomal enzymes were unchanged. A decrease of protein in gastric mucosa was observed 4 and 6 h after indomethacin 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. Famotidine, in spite of its antiulcer effect, failed to prevent the release of NAGA and APh, yet proved to inhibit GLU release. The results suggest that, in addition to their gastroprotective effect, H2-receptor antagonists may contribute to lysosomal membrane protection in indomethacin-induced gastric injury.