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Frog makes its own poison weapons

BETHESDA, Md., April 3 (UPI) -- Scientists said on Wednesday a poisonous Australian frog is the first known to make toxins normally found only in plants, a finding that could lead to new nerve-acting drugs or germ-fighting therapies.

"This was surprising. We didn't expect it," said lead researcher John Daly, a biochemist with the National Institutes of Health in Bethesda.

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In the 1960s, Daly helped discover complex biochemicals called alkaloids in the skins of brightly colored frogs. Natives of Colombia used the alkaloids for centuries to create deadly darts for hunting prey. The frogs harbor toxins in their damp skin as chemical defenses against predators and microbial infections.

Snakes make their own venom or poison but frogs are the only vertebrates known that use alkaloids. Until now, biologists thought all frogs obtained their toxins from by eating insects such as ants and beetles.

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These poisons, usually associated with plants, are lead compounds for the design of novel drugs such as heart stimulants, antibiotics and painkillers. A range of 24 different frog-skin alkaloid classes have been discovered by scientists inspecting hundreds of species from all around the world over the past four decades. The chemicals also often are used as medical research tools to investigate heart function, muscle contraction and nerve conduction.

Daly's group collaborated with biologists at Adelaide University in Australia to study small, colorfully striped frogs known as Pseudophryne that live in forests and grasslands. The amphibians bear two kinds of alkaloids on their skin -- pumiliotoxins, found in poison frogs all over the world, and pseudophrynamines, a completely different alkaloid unique to the Aussie species.

Daly and his team had previously shown poison frogs from South America and Madagascar raised in captivity had no alkaloids in their skin but could secrete them when the biochemicals were provided in their diet. This time, they compared two groups of Pseudophryne -- eight captured from the wild, and 18 raised in captivity.

While the wild frogs had high levels of pumiliotoxins and only trace levels of pseudophrynamines, the captive frogs had high levels of pseudophrynamines in their system and no pumiliotoxins. The diet of the captive frogs was found to be alkaloid-free.

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This means Pseudophryne can make their own chemical weapons while also obtaining it from their food.

"Another possibility is that a symbiotic organism in the frogs is making the pseudophrynamines, but we don't think that's too likely," said researcher Thomas Spande, an organic chemist at NIH.

The pseudophrynamines the frogs generate are potent blockers of nicotinic receptors, which are involved in nerve cell function. Researchers also have believe the chemicals may fight everything from viruses and bacteria.

"Already we've gotten pretty good results that some are antifungal," Spande told UPI. "Maybe that's why they're made by the frogs in the first place -- frogs are in damp places a lot."

Organic chemist Jerrold Meinwald of Cornell University in Ithaca, N.Y., praised Daly's work and said the finding is not necessarily too surprising, given life's diversity.

"It shows that when you seen one frog, you haven't seen them all," Meinwald quipped.

The scientists described their findings in the Journal of Natural Products.

(Reported by Charles Choi in New York.)

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