Polyamines as Snake Toxins and Their Probable Pharmacological Functions in Envenomation.
While decades of research have focused on snake venom proteins, far less attention has been paid to small organic venom constituents. Using mostly pooled samples, we surveyed 31 venoms (six elapid, six viperid, and 19 crotalid) for spermine, spermidine, putrescine, and cadaverine. Most venoms contained all four polyamines, although some in essentially trace quantities. Spermine is a potentially significant component of many viperid and crotalid venoms (≤0.16% by mass, or 7.9 µmol/g); however, it is almost completely absent from elapid venoms assayed. All elapid venoms contained larger molar quantities of putrescine and cadaverine than spermine, but still at levels that are likely to be biologically insignificant. As with venom purines, polyamines impact numerous physiological targets in ways that are consistent with the objectives of prey envenomation, prey immobilization via hypotension and paralysis. Most venoms probably do not contain sufficient quantities of polyamines to induce systemic effects in prey; however, local effects seem probable. A review of the pharmacological literature suggests that spermine could contribute to prey hypotension and paralysis by interacting withN-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, nicotinic and muscarinic acetylcholine receptors, γ-Aminobutyric acid (GABA) receptors, blood platelets, ryanodine receptors, and Ca2+-ATPase. It also blocks many types of cation-permeable channels by interacting with negatively charged amino acid residues in the channel mouths. The site of envenomation probably determines which physiological targets assume the greatest importance; however, venom-induced liberation of endogenous, intracellular stores of polyamines could potentially have systemic implications and may contribute significantly to envenomation sequelae.
Division of Faculty Affairs, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa-ken 904-0495, Japan. steven.aird@oist.jp.|Ecology and Evolution Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa-ken 904-0495, Japan. steven.aird@oist.jp.
Steven D
SD
Aird
Division of Research Support, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa-ken 904-0495, Japan. avillar@oist.jp.
Alejandro
A
Villar Briones
Division of Research Support, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa-ken 904-0495, Japan. mcroy@oist.jp.
Michael C
MC
Roy
Ecology and Evolution Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa-ken 904-0495, Japan. steven.aird@oist.jp.
Alexander S
AS
Mikheyev
cadaverine; envenomation sequelae; pharmacology; polyamines; putrescine; snake venoms; spermidine; spermine; titer
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