The pheromone trail laid down by an Aphaenogaster rudis ant, to help the ant and its recruited nest mates find their way back to prey they plan to kill, contains a chemical now undergoing clinical trials as a possible Alzheimer's disease treatment, Cornell chemists report in the January 1998 issue of the German journal Naturwissenschaften.
Anabaseine, whose chemical analog GTS-21 stimulates the nicotine receptor sites in the brains of Alzheimer's patients and helps reduce memory loss, is one of four components found by Cornell researchers in secretions from the poison glands of A. rudis ants, a common species in the Northeast United States.
"However, this doesn't mean we should grow ants to treat Alzheimer's patients," said Athula B. Attygalle, senior research associate in the Cornell Institute for Research in Chemical Ecology (CIRCE) laboratory of Professor Jerrold Meinwald as well as director of the Mass Spectrometry Facility in Cornell's Department of Chemistry. "Synthetic versions of anabaseine can be made much more easily for medicinal purposes. We're interested in these neurotoxins because they're found in 'lower' animals, such as marine worms and ants, and even plants, and they seem to have an effect on the human brain," Attygalle said.
Friedrich Kern, a visiting scientist in chemistry who observed A. rudis ant behavior in the laboratory as well as in wooded areas near Ithaca, described how one chemical cocktail serves several purposes for the ants.
"This tiny ant needs help subduing prey that can be 10 to 15 times its size, so the ant returns to the nest and tries to recruit some nest mates," Kern explained. "The ant marks the route by dragging its sting along the ground like an ink pen and leaves traces of this four-part chemical cocktail from its poison gland.
"The chemical is a recruitment pheromone," Kern continued, "and when ants sense the pheromone, they become excited enough to follow the trail back to the prey -- perhaps a worm or grub or an adult insect of some kind. Then they attack the prey with their stings, inject a neurotoxin that paralyzes muscles and drag the prey back to the nest."
Ants use receptors on their antennae to follow recruitment pheromone trails. (See the scanning electron microscope image above.)
Gas chromatographic and mass spectrometric analyses in the Cornell laboratory identified four components in the multipurpose fluid from the ants' poison glands. They are N-isopentyl-2-phenylethylamine, a key compound never before identified from nature; anabaseine (3,4,5,6-tetrahydro-2,3'-bipyridine); anabasine [3-(2-piperidinyl)pyridine]; and a fourth chemical never before found in ants, 2,3'-bipyridyl.
Further studies with the ants showed that the four chemicals together act synergistically and that individual chemicals do not induce the same behavioral response. Describing a laboratory experiment with ants following a trail of the four-part cocktail that diverged into four trails of individual components, the chemists reported in Naturwissenschaften: "They searched around, but not a single ant was able to proceed and follow any of the continuation trails."
"As we continue to investigate the roles of chemicals in the lives of various species, we find certain compounds turning up in very different organisms," Attygalle said. "Here we have pyridine-based alkaloids that appear in tobacco leaves, in marine worms as defensive compounds and in ants to help them obtain food."
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