HETEROCYCLES

Review | Special issue | Vol. 79, No. 1, 2009, pp. 277-297
Received, 1st November, 2008, Accepted, 11th December, 2008, Published online, 15th December, 2008.
DOI: 10.3987/REV-08-SR(D)11

■ Arthropod Alkaloids in Poison Frogs: A Review of the ‘Dietary Hypothesis’

Ralph A. Saporito,* Thomas F. Spande, H. Martin Garraffo, and Maureen A. Donnelly

Department of Biological Sciences, Old Dominion University, Norfolk, Virginia 23529, U.S.A.

Abstract

Poison frogs are chemically defended from predators and/or microorganisms by the presence of alkaloids in dermal skin glands. Over the past 40 years, more than 800 alkaloids, which are generally organized into 28 structural classes, have been identified in several lineages of poison frogs worldwide. Originally, the presence of alkaloids in frogs was thought to be the result of biosynthesis, however research led largely by John W. Daly resulted in the discovery that most of these alkaloids are sequestered unchanged from dietary arthropods. In the present paper, we review the most significant findings and studies that led to the proposal of the ‘dietary hypothesis’.

References

1. J. W. Daly, T. F. Spande, and H. M. Garraffo, J. Nat. Prod., 2005, 68, 1556. CrossRef
2. J. W. Daly, B. Witkop, P. Bommer, and K. Biemann, J. Am. Chem. Soc., 1965, 87, 124; CrossRef H. M. Garraffo and T. F. Spande, Heterocycles, 2009, 79, 195. CrossRef
3. C. W. Myers, J. W. Daly, and B. Malkin, Bull. Am. Mus. Nat. Hist., 1978, 161, 307.
4. J. W. Daly, J. Nat. Prod., 1998, 61, 162. CrossRef
5. C. Schöpf, Experientia, 1961, 17, 285. CrossRef
6. G. Habermehl and A. Haaf, Chem. Ber., 1968, 101, 198. CrossRef
7. D. Mebs and W. Pogoda, Toxicon, 2005, 45, 603. CrossRef
8. C. W. Myers and J. W. Daly, Bull. Am. Mus. Nat. Hist., 1976, 157, 173; C. W. Myers and J. W. Daly, Occ. Papers of the Mus. Of Nat. Hist. U. of Kansas, 1976, 59, 1.
9. J. W. Daly, G. B. Brown, M. Mensah-Dwumah, and C. W. Myers, Toxicon, 1978, 16, 163. CrossRef
10. J. W. Daly, C. W. Myers, and N. Whittaker, Toxicon, 1987, 25, 1023. CrossRef
11. C. W. Myers, J. W. Daly, H. M. Garraffo, A. Wisnieski, and J. F. Cover, Jr., Am. Mus. Nov., 1995, 3144, 1.
12. J. W. Daly, C. W. Myers, J. E. Warnick, and E. X. Abuquerque, Science, 1980, 208, 1383. CrossRef
13. J. W. Daly, S. I. Secunda, H. M. Garraffo, T. F. Spande, A. Wisnieski, C. Nishihira, and J. F. Cover, Jr., Toxicon, 1992, 30, 887. CrossRef
14. J. W. Daly, S. I. Secunda, H. M. Garraffo, T. F. Spande, A. Wisnieski, and J. F. Cover, Jr., Toxicon, 1994a, 32, 657. CrossRef
15. T. Tokuyama, J. W. Daly, and B. Witkop, J. Am. Chem. Soc., 1969, 91, 3931. CrossRef
16. T. Grant, D. R. Frost, J. P. Caldwell, R. Gagliardo, C. F. B. Haddad, P. J. R. Kok, D. B. Means, B. P. Noonan, W. E. Schargel, and W. C. Wheeler, Bull. Am. Mus. Nat. Hist., 2006, 299, 1. CrossRef
17. D. F. Johnson and J. W. Daly, Biochem. Pharmacol., 1971, 20, 2555. CrossRef
18. J. W. Daly and C. W. Myers, Science, 1967, 156, 970. CrossRef
19. H. M. Garraffo, T. F. Spande, J. W. Daly, A. Baldessari, and E. G. Gros, J. Nat. Prod., 1993a, 56, 357. CrossRef
20. H. M. Garraffo, J. Caceres, J. W. Daly, T. F. Spande, N. R. Andriamaharavo, and M. Andriantsiferana, J. Nat. Prod., 1993b, 56, 1016. CrossRef
21. M. A. Donnelly, Copeia, 1991, 3, 723. CrossRef
22. B. Tursch, D. Daloze, J. C. Braekman, C. Hootele, and J. M. Pasteels, Tetrahedron, 1975, 31, 1541. CrossRef
23. Note: Because of the large number of alkaloids from anuran skins, all alkaloids have been assigned code names, which consist of a boldfaced number corresponding to the nominal mass and a boldfaced letter for identification of individual alkaloids with the same nominal mass.
24. F. J. Ritter, I. E. M. Rogans, E. Talman, P. E. J. Verwiel, and F. Stein, Experientia, 1973, 29, 530; CrossRef F. J. Ritter and C. J. Persoons, Netherlands J. Zool., 1975, 25, 261. CrossRef
25. T. H. Jones, M. S. Blum, H. M. Fales, and C. R. Thompson, J. Org. Chem., 1980, 45, 4778. CrossRef
26. T. H. Jones, M. S. Blum, H. M. Fales, C. R. F. Brandao, and J. Lattke, J. Chem. Ecol., 1991, 17, 1897. CrossRef
27. T. H. Jones, J. A. Torres, T. F. Spande, H. M. Garraffo, M. S. Blum, and R. R. Snelling, J. Chem. Ecol., 1996, 22, 1221. CrossRef
28. J. Meinwald, J. Smolanoff, A. T. McPhail, R. W. Miller, T. Eisner, and K. Hicks, Tetrah. Lett., 1975, 28, 2367. CrossRef
29. R. A. Saporito, M. A. Donnelly, R. L. Hoffman, H. M. Garraffo, and J. W. Daly, J. Chem. Ecol., 2003, 29, 2781. CrossRef
30. J. W. Daly, H. M. Garraffo, T. F. Spande, C. Jaramillo, and A. S. Rand, J. Chem. Ecol., 1994b, 20, 943. CrossRef
31. H. M. Garraffo, P. Jain, T. F. Spande, J. W. Daly, T. H. Jones, L. J. Smith, and V. E. Zottig, J. Nat. Prod., 2001, 64, 421. CrossRef
32. J. M. Brand, M. S. Blum, H. M. Fales, and J. G. MacConnell, Toxicon, 1972, 10, 259. CrossRef
33. Note: On the basis of unpublished data from the laboratory notebooks of J.W. Daly, it appears that Hyloxalus (= Epipedobates) azureiventris was able to sequester alkaloids that were orally administered in a methanol-saline solution. However, in later experiments4, this species was not able to sequester alkaloids from a diet of alkaloid-dusted fruit flies. Future feeding experiments should be conducted to address this contradiction.
34. J. W. Daly, H. M. Garraffo, T. F. Spande, V. C. Clark, J. Ma, and H. Ziffer, Proc. Nat. Acad. Sci. U.S.A., 2003, 100, 11092. CrossRef
35. J. W. Daly, H. M. Garraffo, G. S. E. Hall, and J. F. Cover, Jr., Toxicon, 1997, 35, 1131. CrossRef
36. B. P. Smith, M. J. Tyler, T. Kaneko, H. M. Garraffo, T. F. Spande, and J. W. Daly, J. Nat. Prod., 2002, 65, 439; CrossRef T. F. Spande, M. W. Edwards, L. K. Pannell, and J. W. Daly, J. Org. Chem., 1988, 53, 1222; CrossRef J. W. Daly, H. M. Garraffo, L. K. Pannell, and T. F. Spande, J. Nat. Prod., 1990, 53, 407. CrossRef
37. W. A. Ayer, M. J. Bennett, L. M. Browne, and J. T. Purdham, Can. J. Chem., 1976, 54, 1807. CrossRef
38. J. W. Daly, H. M. Garraffo, P. Jain, T. F. Spande, R. R. Snelling, C. Jaramillo, and A. S. Rand, J. Chem. Ecol., 2000, 26, 73. CrossRef
39. R. K. Pengilley, J. Zool., 1971, 163, 93. CrossRef
40. P. A. Silverstone, Nat. Hist. Mus. Los Ang. Sci. Bull., 1975, 21, 1; P. A. Silverstone, Nat. Hist. Mus. Los Ang. Sci. Bull., 1976, 27, 1.
41. C. A. Toft, Oecologia, 1980, 45, 131; CrossRef C. A. Toft, Herpetologica, 1995, 51, 202.
42. M. P. Simon and C. A. Toft, Oikos, 1991, 61, 263. CrossRef
43. A. M. Filipello and F. A. Crespo, Cuad. Herpetol., 1994, 8, 18.
44. J. P. Caldwell, J. Zool., 1996, 240, 75. CrossRef
45. M. Vences, F. Glaw, and W. Bohme, Zool. Anz., 1998, 236, 217.
46. T. H. Jones and M. S. Blum, ‘Alkaloids, Chemical and Biological Perspectives, Arthropod Alkaloids: Distribution, Functions and Chemistry’, Vol. 1, ed. by S. W. Pelletier, John Wiley and Sons, NY, 1983, pp 33-84.
47. T. H. Jones, J. S. T. Gorman, R. R. Snelling, J. H. C. Delabie, M. S. Blum, H. M. Garraffo, P. Jain, J. W. Daly, and T. F. Spande, J. Chem. Ecol., 1999, 25, 1179. CrossRef
48. T. F. Spande, P. Jain, H. M. Garraffo, L. K. Pannell, H. C. J. Yeh, J. W. Daly, S. Fukumoto, K. Imamura, T. Tokuyama, J. Torres, R. R. Snelling, and T. H. Jones, J. Nat. Prod., 1999, 62, 5. CrossRef
49. T. H. Jones, H. L. Voegtle, H. M. Miras, R. G. Weatherford, T. F. Spande, H. M. Garraffo, J. W. Daly, D. W. Davidson, and R. R. Snelling, J. Nat. Prod., 2007, 70, 160. CrossRef
50. C. W. Myers and M. A. Donnelly, Am. Mus. Nov., 1996, 3172, 1.
51. C. W. Myers and M. A. Donnelly, Am. Mus. Nov., 1997, 3213, 1.
52. C. W. Myers and M. A. Donnelly, Bull. Am. Mus. Nat. Hist., 2001, 261, 1. CrossRef
53. C. W. Myers and M. A. Donnelly, Bull. Am. Mus. Nat. Hist., 2008, 308, 1. CrossRef
54. J. W. Daly, T. Kaneko, J. Wilham, H. M. Garraffo, T. F. Spande, A. Espinosa, and M. A. Donnelly, Proc. Nat. Acad. Sci. U.S.A., 2002, 99, 13996. CrossRef
55. R. A. Saporito, H. M. Garraffo, M. A. Donnelly, A. L. Edwards, J. T. Longino, and J. W. Daly, Proc. Nat. Acad. Sci. U.S.A., 2004, 101, 8045. CrossRef
56. R. A. Saporito, M. A. Donnelly, R. A. Norton, H. M. Garraffo, T. F. Spande, and J. W. Daly, Proc. Nat. Acad. Sci. U.S.A., 2007, 104, 8885. CrossRef
57. V. C. Clark, C. J. Raxworthy, V. Rakotomalala, P. Sierwald, and B. L. Fisher, Proc. Nat. Acad. Sci. U.S.A., 2005, 102, 11617; CrossRef Y. Kuwahara, N. Mori, and T. Tanabe, Jpn. J. Environ. Entomol. Zool., 2007, 18, 91.
58. W. Takada, T. Sakata, S. Shimano, Y. Enami, N. Mori, R. Nishida, and Y. Kuwahara, J. Chem. Ecol., 2005, 31, 2403. CrossRef
59. T. R. E. Southwood, ‘Ecological methods, with particular reference to the study of insect populations’, Chapman & Hall, London, 2 ed., 1978.
60. Note: The world map in Figure 3 is from “The World Factbook”, operated by the United States of America, Central Intelligence Agency, https://www.cia.gov/library/publications/the-world-factbook/index.html.
61. Note: In 2006, amphibians underwent a major taxonomic revision, and therefore some of the taxonomic information in Figure 3 is out dated (for new taxonomy, see16, 63, 64).
62. Note: As a result of the taxonomic revision of amphibians,61 the number and diversity of frogs listed in Figure 3 has changed, and in general, has increased. However, the general pattern remains the same, with a large number of frogs not having been examined for the presence of alkaloids.
63. D. R. Frost, T. Grant, J. Faivovich, R. H. Bain, A. Haas, C. F. B. Haddad, R. O. De Sa, A. Channing, M. Wilkinson, S. C. Donnellan, C. J. Raxworthy, J. A. Campbell, B. L. Blotto, P. Moler, R. C. Drewes, R. A. Nussbaum, J. D. Lynch, D. M. Green, and W. C. Wheeler, Bull. Am. Mus. Nat. Hist., 2006, 297, 1. CrossRef
64. D. R. Frost, ‘Amphibian Species of the World: an Online Reference’, Electronic Database accessible at http://research.amnh.org/herpetology/amphibia/index.php. American Museum of Natural History, New York, USA, Version 5.2, 2008