TOXINS
WRITTEN BY D.KNIGHT
INTRODUCTION
Dendrobatoids from the superfamily Dendrobatoidea (Dendrobatidae + Aromobatidae) cary a variety of toxins, the skin of the poison dart frog has been found to contain almost 500 different lipophilic alkaloids spanning over 20 different structural classes. The types of toxins include batrachotoxins, pumilioxins, allopumiliotoxins, homopumiliotoxins, gephyrotoxins, and histrionicotoxins most of which have affects on the contraction of muscle cells.
INTRODUCTION
Dendrobatoids from the superfamily Dendrobatoidea (Dendrobatidae + Aromobatidae) cary a variety of toxins, the skin of the poison dart frog has been found to contain almost 500 different lipophilic alkaloids spanning over 20 different structural classes. The types of toxins include batrachotoxins, pumilioxins, allopumiliotoxins, homopumiliotoxins, gephyrotoxins, and histrionicotoxins most of which have affects on the contraction of muscle cells.
TYPES OF TOXINS
Batrachotoxins
The neurotoxin batrachotoxin (BTX) is a member of a family of steroidal alkaloids called batrachotoxins. The batrachotoxin family includes batrachotoxin, homobatrachotoxin, batrachotoxinin A, and pseudobatrachotoxin. This series of toxins is highly potent and is most famously found in Phyllobates terriblis, pound for pound the earths most toxic animal. The concentration of toxin ranges wildly through out the genus Phyllobates, from virtually undetectable up to a whopping 1.9 mg. The does is deadliy a meer 0.05mg is enough to kill a 20 gram mouse. An average P.terriblis contains 1100 mg of compounds, enough to kill upwards of 20,000 mice.
Pumiliotoxins
These toxins are present in all mebers of the genuses Phyllobates and Dendrobates. There are over 100 toxins in this group, but despite the numerous toxins in much is still unknown. The group is split into three, Pumiliotoxins Aand B which are more potent than those of group C. This group of toxins affect the transport of calcium ions in the calcium and sodium dependent processes withing nerve and skeletal muscles (Myers and Daly 1983; Patocka et al. 1999). Pumiliotoxins are often 100 to 1000 times less toxic than their batrachotoxin counterparts.
A 100 grams of either pumiliotoxins A or B in mice caused death in under ten minuets, and even Pumiliotoxin B caused deathin under twenty minuets.
NATURAL SOURCES & HARVESTING
These "Poison" frogs do not produce the toxins themselves, its harvested from the insect which make their diet. Major sources of these toxins are presnt in coresine beetles, which contain batrachotoxins in high concentrations, fire ants which are known to synthesize alkaloids, and a recent discovery suggests that alkaloids may also be obtained from tiny arthropods called oribatid mites. Some poison frogs not only absorb the alkaloids of the insects they consume, but also have the ability to chemically modify certain other toxins and thus create more toxic variants. Dendrobates auratus consumes pumiliotoxin 251D and merely stores it, but some members of the Dendrobatidae family are able to convert 80 percent of ingested pumiliotoxin (+)- 251D to allopumiliotoxin (+)- 267A, which is five times more toxic than the starting material.
Batrachotoxins
The neurotoxin batrachotoxin (BTX) is a member of a family of steroidal alkaloids called batrachotoxins. The batrachotoxin family includes batrachotoxin, homobatrachotoxin, batrachotoxinin A, and pseudobatrachotoxin. This series of toxins is highly potent and is most famously found in Phyllobates terriblis, pound for pound the earths most toxic animal. The concentration of toxin ranges wildly through out the genus Phyllobates, from virtually undetectable up to a whopping 1.9 mg. The does is deadliy a meer 0.05mg is enough to kill a 20 gram mouse. An average P.terriblis contains 1100 mg of compounds, enough to kill upwards of 20,000 mice.
Pumiliotoxins
These toxins are present in all mebers of the genuses Phyllobates and Dendrobates. There are over 100 toxins in this group, but despite the numerous toxins in much is still unknown. The group is split into three, Pumiliotoxins Aand B which are more potent than those of group C. This group of toxins affect the transport of calcium ions in the calcium and sodium dependent processes withing nerve and skeletal muscles (Myers and Daly 1983; Patocka et al. 1999). Pumiliotoxins are often 100 to 1000 times less toxic than their batrachotoxin counterparts.
A 100 grams of either pumiliotoxins A or B in mice caused death in under ten minuets, and even Pumiliotoxin B caused deathin under twenty minuets.
NATURAL SOURCES & HARVESTING
These "Poison" frogs do not produce the toxins themselves, its harvested from the insect which make their diet. Major sources of these toxins are presnt in coresine beetles, which contain batrachotoxins in high concentrations, fire ants which are known to synthesize alkaloids, and a recent discovery suggests that alkaloids may also be obtained from tiny arthropods called oribatid mites. Some poison frogs not only absorb the alkaloids of the insects they consume, but also have the ability to chemically modify certain other toxins and thus create more toxic variants. Dendrobates auratus consumes pumiliotoxin 251D and merely stores it, but some members of the Dendrobatidae family are able to convert 80 percent of ingested pumiliotoxin (+)- 251D to allopumiliotoxin (+)- 267A, which is five times more toxic than the starting material.
EFFECTS
The toxins are excreated though the granular glands of the frogs skin. The glands are surrounded by a discontinuous layer of smooth muscle cells. Most of the gland is filled with membrane-bound granules, early in the secretory cycle, the central part of the gland is filled with flocculent material which appears to be progressively partitioned off by membranes to form the droplet anlage. As granules form, the structure of the contents becomes progressively more vesicular. Dense vesicles, which bud off from the Golgi apparatus, fuse with the granular membrane during the development of granules, and might contain enzymes involved in toxin synthesis. The granules at this point resemble multivesicular bodies. Their structure is similar in all species of dendrobatid frogs even though the different frogs secrete substances of different chemical structure and toxicity.
Most Dendrobatid toxins work in similar ways, the poisonous alkaloids in the frog skin are categorized as neurotoxins. They affect nerves and muscles by causing an irreversible depolarization that blocks signal transmission. The depolarization is caused by opening the sodium channel and allowing sodium ions to rush into the cell and thus eliminating the resting membrane potential necessary for electrical transmission. This results in cardiac arrhythmia, neuromuscular blockage, and death.
Batrachotoxins is an incredibly potent chemical which has the ability to "selectively increase the permeability of the outer membrane of nerve and muscle cells to sodium ions" (Myers and Daly 1983). By preventing the normal closing of these channels within muscle fibers it permits a large influx of sodium into the cell causing an irreversible electrical depolarization. Consequently, nerve signals which under normal circumstances would allow the muscle to relax are blocked and the muscle remains in a contracted state (Myers and Daly 1983). It turns out that the Purkinje cells within the heart are extremely sensitive to this fiber (Albuquerque et al. 1971). Consequently, the toxin causes heart arrhythmias, fibrilation and ultimately failure. Pumiliotoxins cause locomotor difficulties, partial paralysis of hind limbs, salivation, extensor movements, and finally, clonic convulsions and death in less than 10 minutes. Lesser doses or less toxic derivatives initial cause hyperactivity with accompanying hypersensitivity to stimuli and locomotor difficulties, but no death. Histionicotoxins creates a blockage of ions between the end-plate channel and the acetylcholine receptor (Myers and Daly 1983). The toxin prevents ions from flowing from nerve and muscle cells, preventing them from returning to the resting state
The toxins are excreated though the granular glands of the frogs skin. The glands are surrounded by a discontinuous layer of smooth muscle cells. Most of the gland is filled with membrane-bound granules, early in the secretory cycle, the central part of the gland is filled with flocculent material which appears to be progressively partitioned off by membranes to form the droplet anlage. As granules form, the structure of the contents becomes progressively more vesicular. Dense vesicles, which bud off from the Golgi apparatus, fuse with the granular membrane during the development of granules, and might contain enzymes involved in toxin synthesis. The granules at this point resemble multivesicular bodies. Their structure is similar in all species of dendrobatid frogs even though the different frogs secrete substances of different chemical structure and toxicity.
Most Dendrobatid toxins work in similar ways, the poisonous alkaloids in the frog skin are categorized as neurotoxins. They affect nerves and muscles by causing an irreversible depolarization that blocks signal transmission. The depolarization is caused by opening the sodium channel and allowing sodium ions to rush into the cell and thus eliminating the resting membrane potential necessary for electrical transmission. This results in cardiac arrhythmia, neuromuscular blockage, and death.
Batrachotoxins is an incredibly potent chemical which has the ability to "selectively increase the permeability of the outer membrane of nerve and muscle cells to sodium ions" (Myers and Daly 1983). By preventing the normal closing of these channels within muscle fibers it permits a large influx of sodium into the cell causing an irreversible electrical depolarization. Consequently, nerve signals which under normal circumstances would allow the muscle to relax are blocked and the muscle remains in a contracted state (Myers and Daly 1983). It turns out that the Purkinje cells within the heart are extremely sensitive to this fiber (Albuquerque et al. 1971). Consequently, the toxin causes heart arrhythmias, fibrilation and ultimately failure. Pumiliotoxins cause locomotor difficulties, partial paralysis of hind limbs, salivation, extensor movements, and finally, clonic convulsions and death in less than 10 minutes. Lesser doses or less toxic derivatives initial cause hyperactivity with accompanying hypersensitivity to stimuli and locomotor difficulties, but no death. Histionicotoxins creates a blockage of ions between the end-plate channel and the acetylcholine receptor (Myers and Daly 1983). The toxin prevents ions from flowing from nerve and muscle cells, preventing them from returning to the resting state
HUMAN USES
A rare alkaloid extracted from the skin of Epipedobates tricolor may have some medicinal value, Epibatidine is a painkiller 200 times as potent as morphine. Secretions from dendrobatids are also showing promise as muscle relaxants, heart stimulants and appetite suppressants. Natives of the neo tropical rainforests have used these toxins to tip there hunting darts for many centurys, providing them with a great wepon in killing and gathering food.
A rare alkaloid extracted from the skin of Epipedobates tricolor may have some medicinal value, Epibatidine is a painkiller 200 times as potent as morphine. Secretions from dendrobatids are also showing promise as muscle relaxants, heart stimulants and appetite suppressants. Natives of the neo tropical rainforests have used these toxins to tip there hunting darts for many centurys, providing them with a great wepon in killing and gathering food.