Snake envenomation employs three well integrated strategies: prey immobilization via
hypotension, prey immobilization via
paralysis, and prey digestion.
Purines (
adenosine,
guanosine and
inosine) evidently play a central role in the envenomation strategies of most advanced snakes.
Purines constitute the perfect multifunctional toxins, participating simultaneously in all three envenomation strategies. Because they are endogenous regulatory compounds in all vertebrates, it is impossible for any prey organism to develop resistance to them.
Purine generation from endogenous precursors in the prey explains the presence of many hitherto unexplained
enzyme activities in
snake venoms:
5'-nucleotidase,
endonucleases (including
ribonuclease),
phosphodiesterase,
ATPase,
ADPase,
phosphomonoesterase, and
NADase.
Phospholipases A(2),
cytotoxins,
myotoxins, and
heparinase also participate in
purine liberation, in addition to their better known functions.
Adenosine contributes to prey immobilization by activation of neuronal
adenosine A(1) receptors, suppressing
acetylcholine release from motor neurons and excitatory
neurotransmitters from central sites. It also exacerbates
venom-
induced hypotension by activating A(2) receptors in the vasculature.
Adenosine and
inosine both activate mast cell A(3) receptors, liberating vasoactive substances and increasing vascular permeability.
Guanosine probably contributes to
hypotension, by augmenting vascular endothelial cGMP levels via an unknown mechanism. Novel functions are suggested for toxins that act upon
blood coagulation factors, including
nitric oxide production, using the prey's
carboxypeptidases.
Leucine aminopeptidase may link
venom hemorrhagic
metalloproteases and endogenous
chymotrypsin-like proteases with
venom L-amino acid oxidase (LAO), accelerating the latter. The primary function of LAO is probably to promote prey
hypotension by activating
soluble guanylate cyclase in the presence of
superoxide dismutase. LAO's apoptotic activity, too slow to be relevant to prey capture, is undoubtedly secondary and probably serves principally a digestive function. It is concluded that the principal function of L-type Ca(2+) channel antagonists and
muscarinic toxins, in Dendroaspis
venoms, and
acetylcholinesterase in other
elapid venoms, is to promote
hypotension.
Venom dipeptidyl peptidase IV-like
enzymes probably also contribute to
hypotension by destroying vasoconstrictive
peptides such as
Peptide YY,
neuropeptide Y and
substance P.
Purines apparently bind to other toxins which then serve as
molecular chaperones to deposit the bound
purines at specific subsets of
purine receptors. The assignment of pharmacological activities such as transient
neurotransmitter suppression, histamine release and antinociception, to a variety of proteinaceous toxins, is probably erroneous. Such effects are probably due instead to
purines bound to these toxins, and/or to free
venom purines.