INFLUENCE OF PRECURSORS AND INHIBITORS OF THE STEROL PATHWAY ON STEROL AND CARDENOLIDE METABOLISM IN DIGITALIS-LANATA EHRH

The influence of 25-azacycloartanol, an inhibitor of SAM:cycloartenol 24-methyltransferase, and cyproconazole, an experimental triazole know n to inhibit ergosterol biosynthesis in fungi, on cardenolide and phyt osterol accumulation was studied in different Digitalis lanata Ehrh. t issue cultures. The influence of various steroids was also examined. C ardenolide-producing as well as cardenolide-free tissue cultures conta ined free cholesterol, sitosterol, campesterol and stigmasterol. Stigm asterol was the predominant sterol in cardenolide-producing cultures, whereas sitosterol dominated in cardenolide-free tissues. Suspension-c ultured cells had the highest sterol content of the materials analyzed . Cardenolides and 24-alkyl sterols decreased after administration of 25-azacycloartanol, whereas the pool of free cholesterol increased. Cy proconazol influenced mainly the pools of 24-alkyl sterols and cardeno lides; cholesterol contents did not change significantly. The specific ity and toxicity of the inhibitors applied were evaluated. Neither the 12 beta-hydroxylation of beta-methyldigitoxin was influenced, nor was the stimulating effect of 21-hydroxypregnenolone on cardenolide forma tion inhibited. The results presented support the view that 24-alkyl s terols rather than cholesterol are the favoured sterol precursors of t he cardenolides in Digitalis lanata.