Public Release:  Australian frog is first to make its own chemical weapons

American Chemical Society

Researchers have identified an Australian poison frog that makes its own toxin rather than getting it from food sources. It is the first documented case of a vertebrate that generates its own poison alkaloids, complex chemicals that are usually associated with plants, the researchers said.

Poison frogs release alkaloids from their skin to defend against predators. Until now, the researchers believed that all obtained their alkaloids from eating insects.

The discovery was reported in the April 3 Web edition of the Journal of Natural Products, a peer-reviewed publication of the American Chemical Society, the world's largest scientific society. The discovery will also be described April 8 in Orlando, Fla., at the Society's 223rd national meeting.

"This was surprising. We didn't expect it," said John W. Daly, Ph.D., a biochemist with the National Institutes of Health in Bethesda, Md., and lead investigator for the study.

Daly is this year's winner of the Society's Ernest Guenther Award, which recognizes outstanding achievements in natural products chemistry. He will be honored at an award ceremony April 9 in conjunction with the meeting.

Over the past four decades, Daly and colleagues have investigated hundreds of frog species from all over the world and discovered a wide range of biologically active alkaloids, many of which have become widely used as research tools and as lead compounds for the development of drugs, including heart stimulants, antibiotics and pain killers.

Of the over 500 alkaloids they have characterized from frog skin, most are still believed to have originated from an insect food source. Frogs are the only vertebrates known to obtain alkaloids from the diet. While snakes and other vertebrates can make their own venom or poison, these materials are made of toxic proteins or other chemicals, not alkaloids, Daly said.

One class of alkaloids is found only in Australian frogs of the genus, Pseudophryne. Daly's group isolated and determined the structure of this unique class of alkaloids in the 1980s. They named the alkaloids pseudophrynamines after the frog's genus. As with other frog skin alkaloids, researchers assumed that these frogs obtained their alkaloids from eating insects.

The Australian frogs also contained certain pumiliotoxins, a class of alkaloids that Daly now knows is obtained by other frogs from a dietary source. Daly's group had previously shown that poison frogs from South America and Madagascar that were raised in captivity had no alkaloids in their skin but could sequester them when the compounds were provided in the diet.

In order to extend their studies, they began a collaboration with a biologist at Adelaide University in Australia. The study involved analysis of skin alkaloids of eight wild Australian frogs from this genus and 18 captive-raised frogs, all obtained from the same parental lineage at a state park in Australia.

Daly's group found a remarkable difference in the alkaloid distribution among the two test groups. The wild frogs had high levels of a pumiliotoxin and only trace levels of the pseudophrynamines, while the captive frogs had high levels of the pseudophrynamines but no pumiliotoxins. The diet of the captive frogs was shown to be alkaloid-free.

Their conclusion: Frogs of the genus Pseudophryne make their own pseudophrynamines, but like other poison frogs, obtain pumiliotoxins from dietary sources.

Perhaps the best-known poison frogs are the three brightly colored species of Colombia whose skin has been used by certain natives to create deadly darts for hunting prey. It was these frogs that Daly began studying in the 1960s, leading to the discovery of batrachotoxins. Potent activators of sodium ion channels, these alkaloids are now being used to explore key processes in the human body, including nerve conduction, muscle contraction and heart function.

The pseudophrynamines were found to be potent blockers of nicotinic receptors, which are involved in neurological function. The researchers are planning to investigate the alkaloids for other biological activities.

Most frog skin alkaloids are biologically active and many have been developed as biomedical research tools for understanding human disease. Some derivatives show promise as novel medical treatments for chronic pain, heart arrhythmias and other conditions.

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Funding for this study was provided by the National Institutes of Health.

The online version of the research paper cited above was initially published April 3 on the journal's Web site. Journalists can arrange access to this site by sending an e-mail to newsroom@acs.org or by calling the contact person for this release. The research findings will also be described April 8 in Orlando, Fla., at the 223rd national meeting of the American Chemical Society.

John W. Daly, Ph.D., is a biochemist in the Laboratory of Bioorganic Chemistry at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), a part of the National Institutes of Health.

Reporters please note: A digital photo of an Australian poison frog, Pseudophryne corroboree, is available at: http://www.eurekalert.org/images/release_graphics/Pseudophrynecorroboree.jpg

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