Extracellular ATP plays an important role in the physiology of multicellular organisms; however, it is unknown whether unicellular organisms such as yeast also release ATP extracellularly. Experiments are described here which show that releases ATP to the extracellular fluid. This efflux required glucose and the rate was increased dramatically by the proton ionophores nigericin, monensin, carbonyl cyanide -chlorophenylhydrazone and carbonyl cyanide -(trifluoromethoxy)-phenylhydrazone; ATP efflux was also increased by the plasma membrane proton pump inhibitor diethylstilbestrol. The increase in the concentration of extracellular ATP was not due to cell lysis or general disruption of plasma membrane integrity as measured by colony-forming and methylene-blue-staining assays. ATP efflux was strictly correlated with a rise in intracellular cAMP; therefore, the cAMP pathway is likely to be involved in triggering ATP efflux. These results demonstrate that yeast cells release ATP in a regulated manner.


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