Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.69 (botulinum neurotoxin)
 1,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chloroquine and hydroxychloroquine block neuromuscular transmission in isolated tissues from mouse, rat, guinea pig and chick. Blockade is associated with depressed muscle responses to potassium and abolished muscle responses to nicotinic cholinergic agonists. Within certain time and concentration limits, the blocking effects of chloroquine and hydroxychloroquine are reversible. Both drugs antagonize the onset of paralysis caused by botulinum neurotoxin types A and B, but neither drug antagonizes tetanus toxin or beta-bungarotoxin. The ability of chloroquine and hydroxychloroquine to antagonize botulinum toxin is not due to blockade of nicotinic cholinergic receptors. At concentrations that produce neuromuscular blockade, d-tubocurarine does not antagonize botulinum toxin types A and B. Chloroquine causes botulinum toxin to remain at an antitoxin sensitive site. These data could mean that chloroquine acts at the cell membrane to inhibit toxin binding or internalization, or that it acts in the cell interior to inhibit lysosomal processing of toxin. Whatever its action, chloroquine is the most effective antagonist of botulinum toxin yet described.
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PMID:The interaction between aminoquinolines and presynaptically acting neurotoxins. 628 72

Pruriceptive itch originates following activation of peripheral sensory nerve terminals when pruritogens come in contact with the skin. The ability of botulinum neurotoxins (BoNTs) to attenuate transmitter release from afferent terminals provides a rationale for studying its effect on pruritus. This study investigated the effects of BoNT/A1 and BoNT/B1 on mast cell dependent (Compound 48/80:48/80) and independent (Chloroquine:CQ) scratching. C57Bl/6 male mice received intradermal injection of 1.5 U of BoNT/A1, BoNT/B1 or saline 2, 7, 14 and 21 days prior to ipsilateral 48/80 or CQ at the nape of the neck. Ipsilateral hind paw scratching was determined using an automated recording device. The effect of BoNTs on 48/80 mediated mast cell degranulation was analyzed in human and murine mast cells and the presence of SNAREs was determined using qPCR, immunostaining and Western blot. Pre-treatment with BoNT/A1 and BoNT/B1 reduced 48/80 and CQ induced scratching behavior starting on day 2 with reversal by day 21. Both serotypes inhibited 48/80 induced mast cell degranulation. qPCR and immunostaining detected SNAP-25 mRNA and protein, respectively, in mast cells, however, Western blots did not. This study demonstrates the long-lasting anti-pruritic effects of two BoNT serotypes, in a murine pruritus model using two different mechanistically driven pruritogens. These data also indicate that BoNTs may have a direct effect upon mast cell degranulation.
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PMID:A Study and Review of Effects of Botulinum Toxins on Mast Cell Dependent and Independent Pruritus. 2957 Jun 28