Toxins treatment

Tsu et al. [57] have reported that Gz can reconstitute 8 receptor coupling to adenylyl cyclase in HEK 293 cells after pertussis toxin treatment and studies by Law and Reisine [73] have shown that Gz can physically associate with the cloned 8 receptor. Tsu et al. [57] have also shown that Gz can couple the cloned 8 receptor to phospholipase C, providing a potential dual role of this pertussis toxin-insensitive G protein in 8 receptor signaling. 

Taylor, M. J. et al. Increased endotoxin sensitivity following T-2 toxin treatment is associated with increased absorption of endotoxin. Toxicol. Appl. Pharmacol. 109, 51, 1991. 

DETAILS - The toxicity of certain amanita mush rooms has been well known for centuries. The main toxic species in the United States are Amanita phalloides (Deathcupor Destroying Angel), A. verna, and A. virosa. They contain a mixture of the toxins amanitin, phallpidm, and phalloin. Heat weakens or destroys the toxins, as evidenced by the fact that fresh pressed Amanitajuice is three times more toxic than the boiled juice. There is no antidote for these toxins -treatment is largely symptomatic. The liver is the main target ana is virtually destroyed upon short... 

Bums AT, Davies DR, McLaren AJ, Cerundolo L, Morris PJ, Fuggle SV (1998) Apoptosis in ischemia/reperfusion injury of human renal allografts. Transplantation 66(7) 872-876 Carruthers AM, Fozard JR (1993a) Adenosine A3 receptors mediate hypotension in the angiotensin II-supported circulation of the pithed rat. Br J Pharmacol 109(l) 3-5 Carruthers AM, Fozard JR (1993b) Effect of pertussis toxin treatment on the putative adenosine A i receptor-mediated hypotensive response in the rat. Eur J Pharmacol 250( 1) 185—188... 

Naumann M, Jost W (2004) Botulinum toxin treatment of secretory disorders. Mov Disord 19 Suppl 8 S 137 11... 

Got subunits of the Gi/o type of G proteins can be ADP-ribosylated in the presence of pertussis toxin at Cys351, four amino acids from the C-terminus. Petussis toxin sensitivity is the major method of identifying a role for Gai/o proteins in GPCR-mediated signaling. This treatment prevents receptor-mediated G-protein activation and thus exchange of GTP for GDP and so blocks signaling by Ga and G(3y. There are numerous examples of the use of this technique to identify coupling of the delta opioid receptor [e.g., 2,3,41,42,73,77]. One Ga protein in this class, Gaz, lacks the Cys residue that is the site for pertussis toxin action and so is insensitive to pertussis toxin treatment [see 17 for review]. 

Figure 2 Effect of pertussis toxin treatment on the regulation of basal [35S]GTP-yS binding by (2S,3R)TMT-L-Tic in hDOR/CHO cell membranes. Chinese hamster ovary cells stably expressing the human delta opioid receptors (hDOR/CHO) were treated in the presence ( ) or absence ( ) of 50 ng/mL pertussis toxin for 18 h. The cells were washed and cell membranes prepared as previously described [40]. Membranes were incubated with appropriate concentrations of (2S,3R)TMT-L-Tic in the presence of 0.1 nM [35S]GTPyS (1,250 Ci/mmol) in 1.0 mL of assay buffer (25 mM Tris, 150 mM NaCl, 50 iM GDP, 2.5 mM MgCl2, 1 mM EDTA, 30 pM bestatin, 10 pM captopril, pH = 7.4). After 90 min incubation at 30°C, the reaction was terminated by rapid filtration. The filters were washed with 25 mM Tris/120 mM NaCl, pH 7.4, and bound radioactivity was measured by liquid scintillation spectrophotometry.

While the coupling functions of Gs and Gj are well characterized, additional pertussis toxin-sensitive G-proteins (for example G ) have been identified whose functions are still unknown [21]. Interestingly, in certain systems pertussis-toxin treatment prevents the activation of phospholipase C both by hormones and by nonhydrolysable guanine nucleotides [21], Thus, a pertussis-toxin-sensitive G-protein other than Gj (such as Gc) may couple receptors to this transducing enzyme. In other systems activation of phospholipase C is not sensitive to pertussis toxin, indicating that if a G-protein mediates the activation of PLC in these systems, it must be via yet another member of the G-protein family. 

Gronier B, Rasmussen K. 1999. Pertussis toxin treatment differentially affects cholinergic and dopaminergic receptor stimulation of midbrain dopaminergic neurons. Neuropharmacology 38 1903-1912. 

Campos EC, Schiavi C, BeUusci C. Critical age of bomlinum toxin treatment in essential hifantile esotropia. J Pediatr Ophthalmol Strabismus 2000 37 328-332. 

Holmes JM, Beck RW, Kip KE, et al. Botulinum toxin treatment versus conservative management in acute traumatic sixth nerve palsy or paresis. JAAPOS 2000 4 145-149. 

Scott AB, Magoon E, McNeer K, et al. Bomlinum toxin treatment of strabismns in children. Trans Am Ophthalmol Soc 1990 87 174-180. 

Generalized weakness has been reported after botulinum toxin treatment in a patient with amyotrophic lateral sclerosis (18). 

Stell R, Coleman R, Thompson P, Marsden CD. Botulinum toxin treatment of spasmodic torticollis. BMJ 1988 297(6648) 616. 

Simpson LL. The effects of acute and chronic botulinum toxin treatment on receptor number, receptor distribution and tissue sensitivity in rat diaphragm. J Pharmacol Exp Ther 1977 200(2) 343-51. 

Lin MC, Welton AF, Berman MF (1978) Essential role of GTP in the expression of adenylate cyclase activity after cholera toxin treatment. In J. Cycl. Nuc. Res. 4 159-168. 

The relationship between actin polymerization and cell motility was examined by Verschueren et al. (1995). Using a lymphoma-derived cell line, they showed that C2 toxin treatment greatly diminished pseu-dopodal protrusion as well as the ability to invade a monolayer of fibroblast-like cells. This is a predictable finding, and one that must be due at least in part to loss of actin filaments. 

Skin decontamination with soap and water or the hypochlorite solution is capable of effective removing toxin up to six hours after exposure, although none of them neutralize the toxin. Treatment of respiratory, dermal and GI effects currently must be symptom based and supportive in nature. 

It is not understood clearly, however, why sprouting occurs predominantly from nerve terminals following botulinum toxin treatment, whereas sprouting occurs from both nodes of Ranvier and terminals in nerve regeneration. An IGF dose effect on axons might be responsible, because IGF-I and IGF-II mRNAs are increased in nerve and IGF-II mRNA in muscle, during nerve regeneration. By contrast, one would not expect botulinum toxin to increase IGF mRNA content in nerves. 

It has now been found that the ADP-ribose moiety of nicotinamide adenine dinucleotide is also transferred onto some pro-teins. " When histone serves as an acceptor, several ADP-ribose units are transferred in succession, so that a short chain of oligo-(ADP-ribose), linked covalently to the protein, is formed. In another reaction, transferase II, a soluble enzyme involved in protein synthesis in mammalian cells, acts as an acceptor of a single ADP-ribose unit in the presence of diphtheria toxin. - Treatment of the product with venom pyrophosphatase releases adenosine 5 -monophosphate, but the D-ribose 5-phosphate portion still remains attached to the protein it is, therefore, assumed that the linkage involves C-1 of D-ribose. The transferase II that carries the ADP-ribose unit is completely inactive, but it can be reactivated by incubating with nicotinamide and diphtheria toxin. Under these conditions, the reaction is reversed, generating free transferase II protein and nicotinamide adenine dinucleotide. Thus, diphtheria toxin was shown to have a very specific transglycosylase activity the mechanism of this reaction has been studied in detail. ... 

One of the earliest effects found for PGEj was its ability to inhibit epinephrine-induced lipolysis in adipocytes by preventing the accumulation of cAMP ". The ability of PGEj to blunt isoproterenol-induced increases in cAMP in hamster adipocytes was subsequently shown to be reduced in hamsters that had been treated with a crude source of pertussis toxin. More recently, Murayama and Ui demonstrated that pertussis toxin treatment of adipocytes also diminishes the ability of PGEj to cause a GTP-dependent inhibition of adenylate cyclase activity in membranes prepared from these cells associated with this latter effect is a pertussis toxin-dependent, ADP-ribosylation of a protein subunit having the characteristic size (M = 41000) of the subunit of the inhibitory guanine nucleotide regulatory protein N. ... 

No specific therapy for trichothecene mycotoxin poisoning is currently available. Skin decontamination with soap and water or the hypochlorite- (M258A1) or resin-based (M291) military decontamination kits can effectively remove toxin up to six hours after exposure, although none of them neutralize the toxin. Treatment of respiratory, dermal, and GI effects currently must be symptom based and supportive in nature. Superactive activated charcoal, for example, a common treatment for many orally taken poisons, has been shown to bind 0.48 mg T-2/gm charcoal in mice and improve survival rates significantly. 

C. botulinum, dengue, Ebola, EEE, Lassa, plague, Q-fever, ricin, SEB, smallpox, T-2 mycotoxin, tularemia, VEE, and WEE. Other entries involve broader treatments of more than one bacteria, virus, or toxin. Treatments for viruses, C. botulinum, and T-2 mycotoxin account for 35% of the treatment entries in the inventory (13%, 12%, and... 

It has been established however that signaling is not an absolute requirement since pertussis toxin treatment which inhibits Gj-mediated signaling does not prevent infection (16). In addition mutant receptors that do not signal still function as coreceptors (7). Neither is internalization of the chemokine receptor a requisite for infection since C-terminal truncated CXCR4 receptors that are unable to internalize upon ligand binding also still function as coreceptors (8). 

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