Long-chain alkyl ester of AMP acts as an antagonist of glucose-induced signal transduction that mediates activation of plasma membrane proton pump inSaccharomyces cerevisiae

One of the long-chain alkyl esters of AMP, adenosine 5'-hexadecylphosphate (AMPC16), exhibited a cytotoxic growth inhibitory effect on cells of variou s yeast strains, The growth inhibitory effect of AMPC16 on Saccharomyces ce revisiae cells was observed only in medium containing Mg2+, which accelerat ed cellular uptake of the nucleotide analogue, In the presence of Mg2+, AMP C16 completely inhibited glucose-induced extracellular acidification by the intact cells and also interfered with activation of the plasma membrane AT Pase, but did not directly inhibit the ATPase activity itself, AMPC16 treat ment prevented cells from increasing their intracellular sn-1.2-diacylglyce rol (DAC) level in response to glucose, whereas the inhibition of proton ex trusion by the cells could be largely reversed by the coaddition of a membr ane-permeable DAG analogue. The DAC analogue, a physiological activator of protein kinase C (PKC), was not protective against the inhibition of glucos e-induced proton extrusion by staurosporine. which is capable of directly i nterfering with the action of PKC, These results implied that AMPC16 caused a Mg2+-dependent cytotoxic effect on Sac. cerevisiae cells by interfering with a phosphatidylinositol type of signal that mediates activation of the plasma membrane proton pump.