The effects of aspirin and other non-steroid anti-inflammatory/analgesic drugs on gastro-intestinal mucus glycoprotein biosynthesis in vivo: relationship to ulcerogenic actions.

Aspirin and certain other ulcerogenic non-steroid antiinflammatory (NSAI) drugs inhibit the incorporation in vivo of ³⁵S]sulphate into the mucus glycoproteins isolated from the gastric mucosa of rats. Some NSAI drugs, which are shown to be relatively non-ulcerogenic in a sensitive gastric ulcer assay and the analgesic drugs paracetamol and dextropropoxyphene (which are non-ulcerogenic) did not inhibit the biosynthesis of sulphated mucus glycoproteins in vivo. A relationship is therefore shown between the ulcerogenicity of NSAI drugs and the inhibitory effects on gastric mucus biosynthesis. Some potent intestinal ulcerogens (e.g. indomethacin) also inhibit the incorporation of ³⁵S]sulphate into the glycoproteins from the upper intestinal mucosa. Aspirin in contrast stimulates the incorporation of ³⁵S]sulphate into intestinal mucus glycoproteins. The inhibition of the biosynthesis of sulphated gastric mucus glycoproteins by aspirin is shown to (1) depend on the presence of high concentrations of salicylates in the mucosal tissue, (2) be as a consequence of combined inhibitory capacity of aspirin, salicylate and possibly traces of metabolites in the mucosa and (3) be due to an inhibition of the sulphotransferase activity in vitro. Aspirin also inhibits the incorporation into gastric glycoproteins of ¹⁴C]acetate, but not ¹⁴C]threonine, but the effect on ¹⁴C]acetate incorporation may be due to the redistribution of the isotope in vivo.