Biologists at University of California, San Diego (UCSD) have discovered that the popular sedative Valium has similar effects on the social amoeba Dictyostelium discoideum as it does in humans. Their surprising finding that Valium, as well as a "natural Valium" molecule found in human brains, causes the social amoeba to enter a dormant or "sleep" phase, may provide new insights into how cells in higher organisms, including humans, communicate with each other.
The study, published this week in the early on-line edition of Proceedings of the National Academy of Sciences and to appear in the print edition of PNAS May 24th, describes the discovery of a short protein, or peptide, known as SDF-2, that neighboring cells of Dictyostelium use to synchronize the formation of spores - the dormant phase of the organism. The researchers were surprised to find that SDF-2 is similar to a “natural Valium” peptide - called DBI - that is found in human brains. Both DBI and Valium cause Dictyostelium to form spores.
“It was amusing to discover that Valium puts Dictyostelium to sleep and Valium puts humans to sleep,” said William Loomis, a professor of biology at UCSD, who led the study. “But more significantly, our findings confirm that Dictyostelium is an excellent experimental system for studying aspects of communication between cells that are not easily amenable to study in complex multicellular organisms.”
Loomis and Christophe Anjard, an assistant project scientist in Loomis’ laboratory, and first author on the paper, also speculate that spore formation in Dictyostelium might provide a rapid way to screen for new drugs that mimic the anti-anxiety effects of Valium in humans.
“Both DBI and Valium induce spore formation in Dictyostelium, and flumazenil, a drug that inhibits the effects of Valium in humans, inhibits spore formation,” explained Anjard. “Using Dictyostelium to screen for drugs that function like Valium would be very cheap and could identify potential drugs within hours.”
Individual cells of Dictyostelium usually live independently, but when food is scarce the cells form spores. During spore formation, up to one hundred thousand cells cooperate with each other to form a stalk that resembles a golf tee. The formation of spores must be carefully regulated because prior to turning into spores, cells need to climb to the top of the stalk, where they can be more easily dispersed by the wind.
The researchers inferred that cells at the base of the stalk cut up a longer protein to produce the SDF-2 peptide. They said that there is much to be learned about how DBI is made from its longer protein precursor, and what role that longer protein may play in human cells.