PMID- 11738231
OWN - NLM
STAT- MEDLINE
DCOM- 20020322
LR  - 20230411
IS  - 0041-0101 (Print)
IS  - 0041-0101 (Linking)
VI  - 40
IP  - 4
DP  - 2002 Apr
TI  - Ophidian envenomation strategies and the role of purines.
PG  - 335-93
AB  - 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.
FAU - Aird, Steven D
AU  - Aird SD
AD  - Laboratorio de Toxinas Naturais, Universidade Estadual do Ceara, Avenida 
      Paranjana, 1700, Itaperi, 60740-000, Fortaleza, CE, Brazil. sdaird@erols.com
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Toxicon
JT  - Toxicon : official journal of the International Society on Toxinology
JID - 1307333
RN  - 0 (Purines)
RN  - 0 (Toxins, Biological)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Animals
MH  - Digestive System/pathology
MH  - Drug Interactions
MH  - Hemostasis
MH  - Hypotension/etiology/*physiopathology
MH  - Nitric Oxide
MH  - Paralysis/physiopathology
MH  - Purines/chemistry/*pharmacology
MH  - Snake Bites/*physiopathology
MH  - *Snakes
MH  - Toxins, Biological/adverse effects/pharmacology
RF  - 817
EDAT- 2001/12/12 10:00
MHDA- 2002/03/23 10:01
CRDT- 2001/12/12 10:00
PHST- 2001/12/12 10:00 [pubmed]
PHST- 2002/03/23 10:01 [medline]
PHST- 2001/12/12 10:00 [entrez]
AID - S004101010100232X [pii]
AID - 10.1016/s0041-0101(01)00232-x [doi]
PST - ppublish
SO  - Toxicon. 2002 Apr;40(4):335-93. doi: 10.1016/s0041-0101(01)00232-x.