Biology Reference
In-Depth Information
the muscles rest. Due to irreversible binding of anatoxin-a to acetylcholine receptor, constant fl ow
of sodium ions to muscle cells results in membrane depolarization. This causes to open up voltage
sensitive Ca
2+
and Na
2+
channels. The latter may then amplify the response activating further electrical
transmission (Soliakov
et al
., 1995) leading to overstimulation of muscle cells. When respiratory
muscles are involved it results in lack of O
2
to brain leading to convulsions, suffocation and fi nally
death (Mazur-Marzec, 2006).
Lowest dose of anatoxin-a causing death in mice (i.p; LD
10
) was 200-250 µg kg
-1
body weight
(Stevens and Krieger, 1989, 1991) and LD
50
of anatoxin-a was 375 µg kg
-1
body weight (Fitzgeorge
et al
.,
1994). The i.v. LD
50
values were less than 100 µg kg
-1
body weight. LD
50
values for oral administration
and intranasal LD
50
in mice were 5000 and 2000 µg kg
-1
body weight, respectively (Fitzgeorge
et al
.,
1994). Although there are very few studies on toxicity of anatoxin-a, it is worthwhile to mention
the studies of Astrachan
et al
. (1980) who suggested that doses of 200 or 125 µg kg
-1
body weight of
anatoxin-a given thrice a day caused foetal malformation in hamsters.
The binding of anatoxin-a to the acetylcholine receptor sites with greater specifi city has
been demonstrated by the competitive inhibition of [H
3
]-acetylcholine and d-[H
3
]-turbocurarine
binding to the receptor site. The binding of anatoxin-a to receptor site of acetylcholine brings about
conformational changes in the receptor-ion channel complexes. These conformational changes
can be detected by the binding of certain compounds that block neuromuscular transmission
without interacting with receptor site. The binding of certain ion channel blockers such as tritiated
perhydrohistrionicotoxin (H
12
-HTX) and phenylcyclidine (PCP) to the receptor-ion channel complex
is stimulated by anatoxin-a. Aronstam and Witkop (1981) demonstrated that the binding ion-
channel blockers such as H
12
-HTX, PCP and phenylcylcidine methiodide is stimulated in presence
of anatoxin-a to the acetylcholine receptor of
Torpedo
electric tissue.
Two nicotinic acetylcholine-binding sites were evaluated for binding by 18 analogues of
anatoxin-a that differed in side chain structure. Anatoxin-a is the most potent competitor for ligand
binding at [H
3
] nicotine and [
125
I]α-bungarotoxin-binding sites. All analogues have higher affi nity
at [H
3
] nicotine site compared to [
125
I]α-bungarotoxin-binding site (Wonnacott
et al
., 1991).
The toxicity of anatoxin-a is 10-fold more potent than its optically inactive isomer in increasing
mean arterial blood pressure and heart rate, pO
2
and pCO
2
of blood and pH. Severe hypoxemia
and hypercapnia accompanied by acidosis were induced by anatoxin-a by 6 and 4 fold greater than
its optical isomer (Adeyemo and Siren, 1992). A comparison of the effects of anatoxin-a in four
different preparations revealed that anatoxin-a was 50 times more potent than nicotine and 20 times
more potent than acetylcholine (Thomas
et al
., 1993). These studies are supported by the potency
of anatoxin-a in evoking 1A or type 2 current responses in rat hippocampal neurones far greater
than nicotine or acetylcholine (Atkondon and Abulquerque, 1995). Similar to nicotine, anatoxin-a
shows more potency than noradrenaline in releasing dopamine for strial nerve terminals from rat
superfused hippocampal synaptosomes (Clarke and Reuben, 1996). Studies on genotoxic potential of
anatoxin-a are not avilable.
A benthic species of
Oscillatoria
that produced anatoxin-a was shown to
be responsible for dog deaths, after consumption of water on the shores of Loch Insh, Scotland. The
presence of the cyanobacterium in the stomach contents, their positive neurotic response in bioassay
studies and
in vitro
production of anatoxin-a by the cultures of
Oscillatoria
emphasized the role of
anatoxin-a (Edwards
et al
., 1992). Developmental toxicity of anatoxin-a has been studied in pregnant
mice by administering anatoxin-a i.p. (125 or 200 µg kg
-1
body weight) on gestation days (GD), i.e.
8-12 or 13-17 days. Decreased motor activity was observed at 200 µg kg
-1
body weight at both time
