In vitro studies on the effect of salicylates on the synthesis of proteins by guinea pig gastric mucosal tissue.

In the work reported in this paper we have studied the effect of salicylates on protein synthesis by (A) intact guinea pig gastric mucosa, (B) isolated gastric epithelial cells of guinea pig stomach and (C) cell-free homogenates of the isolated cells. In experiments on intact gastric mucosa, (A), secretion of newly-synthesised proteins into the mucosal media was also investigated and the nature of the effected, secreted proteins examined by isopycnic CsCl gradient fractionation. Results indicate that synthesis of proteins, as assessed by incorporation of L-[U-14C]leucine into trichloroacetic acid-insoluble proteins, is significantly impaired in the presence of salicylates in all three systems investigated. In experiments using isolated epithelial cells and cell-free homogenates of these cells, the effect was found to be dose-dependent and not associated with a corresponding reduction of the uptake of the precursor from the medium into the acid-soluble intracellular pool. The inhibitory effect of salicylates on protein synthesis was found to be reversible in experiments using both the intact gastric mucosa, as also the isolated epithelial cell preparations. In all experiments it was found to last for the duration of exposure of the tissue to the action of the drug. In experiments using intact gastric mucosa secretion of the newly-synthesised radioactive proteins into the mucosal medium was also impaired by O-acetyl salicylic acid. Isopycnic CsCl gradient fractionation of the secreted proteins did not reveal any qualitative differences between the salicylate-treated samples and the control samples, indicating non-specific inhibition of protein synthesis by the drug.