ABSTRACT
Purine nucleosides were rst discovered as constituents of snake venoms more than 50 years ago. Despite the fact that relatively little attention has been paid to them, nucleosides are among the most elegant and versatile toxins. They exert synchronous effects upon virtually all cell types, contributing simultaneously to prey immobilization via hypotension, prey immobilization via paralysis, and prey digestion. Because purine nucleosides have similar pharmacological roles in all vertebrates, they are useful against all prey classes, and it is impossible for any prey organism to develop resistance to them. In a sense, purine nucleosides represent the trump card in the competitive predator-prey relationship (increasing toxicity vs. increasing resistance). The pyrimidine nucleosides cytidine and uridine are also widely distributed among snake venoms, but thymidine has not been found in any to date. In contrast to viperine and elapid venoms, crotaline venoms are virtually devoid of nucleosides, suggesting that pit vipers rely upon the enzymatic release of endogenous prey nucleosides. Quantities of venom injected by various venomous snakes in predatory strikes may be used to predict the potential plasma levels of circulating nucleosides achievable as a result of injected venom nucleosides. These levels are more than adequate to activate physiological processes
I. Historical Background ......................................................................................................... 394 II. Role of Purines in Envenomation ......................................................................................... 394 III. The Elegance of Purine Nucleosides as Toxins ................................................................... 395 IV. Purine Generation from Endogenous Precursors ................................................................. 395 V. Recent Studies ...................................................................................................................... 396 A. Venom Mononucleotides ................................................................................................400 B. Venom Pyrimidines ........................................................................................................400 1. Cytidine Pharmacology .............................................................................................400 2. Uridine Pharmacology ...............................................................................................402 C. Venom Purines ...............................................................................................................403 1. Hypoxanthine Pharmacology ....................................................................................403 2. Inosine Pharmacology ...............................................................................................403 3. Guanosine Pharmacology ..........................................................................................404 D. Unidentiable Purines ....................................................................................................404 E. Venom Enzymes That Release Purines ..........................................................................405 VI. Pharmacological Signicance of the Quantities of Nucleosides Found in Venoms ............405 VII. Pharmacology of Deoxyribonucleosides ..............................................................................406 VIII. Conclusions .......................................................................................................................... 411 Acknowledgments .......................................................................................................................... 411 References ...................................................................................................................................... 411
consonant with snake envenomation strategies. Deoxyribonucleosides, such as would be liberated from DNA, by phosphodiesterase and 5′-nucleotidase, have been little explored pharmacologically; however, current data suggest that deoxyribonucleosides have biological activities similar to those of ribonucleosides, although their potencies vary.
