Short communication

The occurrence of l-leucyl-β-naphthylamide (LNA) splitting enzymes in some amphibia and reptile venoms

The present study examined the taxonomic distribution of dipeptidyl peptidase IV (DPP IV) activity in venoms of 59 ophidian taxa, representing seven subfamilies of the Families Elapidae and Viperidae. DPP IV activity is extremely variable at all taxonomic levels. It ranged from essentially none in laticaudine, hydrophiine, and some bungarine and elapine venoms, to 10.72 μmol 4-methoxy-β-naphthylamine liberated per min per 200 μg venom, for Ophiophagus hannah. Intra- and interpopulational variation were examined among eight populations of prairie rattlesnakes (Crotalus viridis viridis), Great Basin rattlesnakes (Crotalus viridis lutosus) and southern Pacific rattlesnakes (Crotalus viridis helleri). Among these populations, the mean weighted range of variation was 4.9-fold, and even among litter mates of C. v. lutosus, DPP IV activity varied as much as 5.6-fold. The two most salient findings, the near ubiquity of DPP IV in snake venoms and its great quantitative variability, even among full siblings, are paradoxical. The widespread distribution of the enzyme suggests an important role in envenomation, while the variable activity levels suggest that DPP IV and by extension, other individual enzymatic constituents, may not be under much individual selective pressure.

Cutaneous granular glands are a shared character of adult amphibians, including caecilians, and are thought to be the source of most biologically active compounds in amphibian skin. Data are available from one or more species in over 100 of nearly 400 genera comprising the three living orders of Amphibia. Many species contain unidentified substances judged to be noxious based on predator aversion or human taste. Additionally, there is a great diversity of known compounds, some highly toxic as well as noxious, which can be tabulated under four broad categories: biogenic amines, peptides, bufodienolides (bufogenins) and alkaloids. The last category includes alkaloids derived from biogenic amines, water-soluble alkaloids (tetrodotoxins) and lipophilic alkaloids. Most compounds are known only from skin of adult amphibians, but the toxic and noxious properties of eggs and larvae of certain salamanders and toads can be attributed to tetrodotoxins and bufodienolides, which occur also in adult tissues other than skin. Predator aversion and various antipredator behaviors and aposematic colorations clearly prove the defensive value of these diverse metabolites, whether or not they are elaborated primarily (e.g. alkaloids) nor secondarily (e.g. some peptides and biogenic amines) for this function.

Lipophilic alkaloids include the samandarine alkaloids, known definitely only from an Old World genus of salamanders, and the more than 200 dendrobatid alkaloids. Nearly all the latter are unique to neotropical poison frogs of the genera Dendrobates and Phyllobates (Dendrobatidae), except for seemingly homoplastic occurrences of a few such alkaloids in small brightly colored anurans of several other families. Owing to recent discoveries and new structural information, the dendrobatid alkaloids are here partitioned among the following major and minor classes: batrachotoxins, histrionicotoxins, indolizidines, pumiliotoxin-A class and its allopumiliotoxin and homopumiliotoxin subclasses, decahydroquinolines, gephyrotoxins, 2,6-disubstituted piperidines, 2,5-disubstituted pyrrolidines, pyridyl-piperidines, indole alkaloids, azatricyclododecenes and amidine alkaloids. Except for the steroidal batrachotoxins, and the minor classes of pyrrolidine alkaloids, indole alkaloids and amidine alkaloids, all the above contain a piperidine ring. A large number of piperidine-based alkaloids occur mainly as trace compounds in Dendrobates and remain unclassified; the only water-soluble toxin so far discovered in a dendrobatid (Colostethus) is structurally unknown, but conceivably an alkaloid.

A. Mar and H. Michl. A study of the high molecular weight hemolysin from the skin secretion of the amphibian Bombina variegata. Toxicon14, 191–195, 1976.—The high molecular weight hemolysin in the toxin of Bombina variegata was characterized by some chemical and physico-chemical properties and compared with other hemolysins of animal or microbial origin. It is markedly different from snake venom direct lytic factors by its molecular weight and acidic character. The time course of hemolysis is sigmoidal and recalls the reaction kinetics of nematocyst hemolysins (Hessinger and Lenhoff, Archs Biochem. Biophys.159, 629, 1973a). Free SH-groups are not responsible for the binding to the cell surface. The activity of the hemolysin depends on Ca²⁺ ions.