tautomycin and dinophysistoxin-1

Effects of compounds of the okadaic acid type (okadaic acid, dinophysistoxin-1, calyculin A and tautomycin) on proliferation by digestive-tract epithelial cells were investigated in mice and rats. In mice, a single oral administration of these agents caused significant enhancement of BrdU labeling indices in a dose/response manner. Exceptions showing no response were limited to the pyloric mucosa for okadaic acid, the pyloric and fundic mucosa for calyculin A and the pyloric mucosa for tautomycin. Sequential analysis of labeling indices after a single oral administration of dinophysistoxin-1 revealed two peaks of cell proliferation at 18 h and 36 h in the esophagus, ileum and colon. The labeling indices of the forestomach, fundus, pylorus and jejunum, on the other hand, continuously increased from 6 h after the administration. Elevated proliferation was also observed in the skin after 30 h or after, but no effects on the liver or kidney were evident. A single oral administration of the okadaic acid type of compounds also dose-dependently enhanced cell proliferation of the rat digestive tract. These results strongly suggest that the okadaic acid class of compounds may exert promoting potential for the gastrointestinal mucosa when administered orally.

Topics: Administration, Oral; Animals; Antifungal Agents; Bromodeoxyuridine; Carcinogens; Cell Division; Dose-Response Relationship, Drug; Ethers, Cyclic; Intestinal Mucosa; Male; Marine Toxins; Mice; Mice, Inbred ICR; Okadaic Acid; Oxazoles; Pyrans; Rats; Rats, Sprague-Dawley; Spiro Compounds; Time Factors

The effects of tautomycin, a protein phosphatase inhibitor, on recycling of cell surface molecules were studied with transferrin receptor (TFR) of human myeloid leukemia K562 cells and with CD4 of murine thymocytes. Tautomycin increased expression of TFR of K562 cells whereas phorbol dibutylate (PDBu) decreased it. Tautomycin inhibited PDBu-induced down-regulation of CD4 although it did not induce up-regulation. Okadaic acid also inhibited down-regulation of CD4 which was induced by PDBu. The results suggest that certain inhibitors of protein phosphatases preferentially inhibit endocytosis of cell surface molecules.

Topics: Alkaloids; Antifungal Agents; Carbazoles; CD4 Antigens; Down-Regulation; Ethers, Cyclic; Indole Alkaloids; Okadaic Acid; Phorbol 12,13-Dibutyrate; Protein Kinase C; Pyrans; Receptors, Transferrin; Spiro Compounds; Staurosporine