The inveterate botulinum neurotoxin A ushers in exo-endocytic crypts

Potian, Joseph G.; Patel, Vikas; McArdle, Joseph J.; Thyagarajan, Baskaran

doi:10.1504/tbj.2010.039116

Cited by 4 publications

(3 citation statements)

References 21 publications

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“…WMN suppresses PIP2 by inhibiting PI Kinase enzyme activity. WMN treatment caused delocalization of clathrin heavy chain ((Potian et al, 2010) and suppressed the EPC and quantal content of diaphragm NMP (Fig. 7).…”

Section: 0 Discussionmentioning

confidence: 90%

“…Previous research work demonstrates that inhibition of PI3 kinase slows down endocytosis (Richards et al, 2004). Further, WMN treatment has been shown to inhibit clathrin-dependent endocytosis of neurotoxin by delocalizing endocytic proteins (Potian et al, 2010). If the endocytic mechanisms couple to exocytosis, then WMN treatment should suppress exocytosis.…”

Section: 0 Resultsmentioning

confidence: 99%

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Capsaicin modulates acetylcholine release at the myoneural junction

Thyagarajan

Potian

Baskaran

et al. 2014

European Journal of Pharmacology

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Transient receptor potential (TRP) proteins are non-selective cation channel proteins that are expressed throughout the body. Previous studies demonstrated the expression of TRP Vanilloid 1 (TRPV1), capsaicin (CAP) receptor, in sensory neurons. Recently, we reported TRPV1 expression in mouse motor nerve terminals [MNTs; (Thyagarajan et al., 2009)], where we observed that CAP protected MNTs from botulinum neurotoxin A (BoNT/A). Phrenic nerve diaphragm nerve muscle preparations (NMP) isolated from isoflurane anesthetized adult mice were analyzed for twitch tension, spontaneous (mEPCs) and nerve stimulus evoked (EPCs) acetylcholine release. When acutely applied to isolated NMP, CAP produced a concentration-dependent decline of twitch tension and produced a significant decline in the amplitude of EPCs and quantal content without any effect on the mEPCs. The suppression of nerve stimulus evoked acetylcholine release by CAP was antagonized by capsazepine (CPZ), a TRPV1 antagonist. CAP did not suppress phrenic nerve stimulus evoked acetylcholine release in TRPV1 knockout mice. Also, CAP treatment, in vitro, interfered with the localization of adapter protein 2 in cholinergic Neuro 2a cells. Wortmannin, (WMN; non-selective phosphoinositol kinase inhibitor), mimicked the effects of CAP by inhibiting the acetylcholine exocytosis. Our data suggest that TRPV1 proteins expressed at the MNT are coupled to the exo-endocytic mechanisms to regulate neuromuscular functions.

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Section: 0 Discussionmentioning

confidence: 90%

Section: 0 Resultsmentioning

confidence: 99%

Capsaicin modulates acetylcholine release at the myoneural junction

Thyagarajan

Potian

Baskaran

et al. 2014

European Journal of Pharmacology

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“…Direct inhibition of clathrincoated pit-dependent uptake of BoNT/A was first shown in vitro by Potian In support of this result, local hind limb injection of wortmannin was shown to protect mice from BoNT/A-mediated neuroparalysis (Potian et al 2010a). This set the trend for research strategies to interfere with the uptake of neurotoxins at the MNT.…”

Section: Toxin Endocytosis Inhibitorsmentioning

confidence: 78%

Biological Toxins and Bioterrorism

Gopalakrishnakone¹,

Balali-Mood²,

Llewellyn³

et al. 2015

Toxinology

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In recent years, the field of toxinology has expanded substantially. On the one hand it studies venomous animals, plants and micro organisms in detail to understand their mode of action on targets. While on the other, it explores the biochemical composition, genomics and proteomics of toxins and venoms to understand their three interaction with life forms (especially humans), development of antidotes and exploring their pharmacological potential. Therefore, toxinology has deep linkages with biochemistry, molecular biology, anatomy and pharmacology. In addition, there is a fast-developing applied subfield, clinical toxinology, which deals with understanding and managing medical effects of toxins on human body. Given the huge impact of toxin-based deaths globally, and the potential of venom in generation of drugs for so-far incurable diseases (for example, diabetes, chronic pain), the continued research and growth of the field is imminent. This has led to the growth of research in the area and the consequent scholarly output by way of publications in journals and books. Despite this ever-growing body of literature within biomedical sciences, there is still no all-inclusive reference work available that collects all of the important biochemical, biomedical and clinical insights relating to toxinology. Composed of 11 volumes, Toxinology provides comprehensive and authoritative coverage of the main areas in toxinology, from fundamental concepts to new developments and applications in the field. Each volume comprises a focused and carefully chosen collection of contributions from leading names in the subject.

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Antidotes to Botulinum Neurotoxin

Thyagarajan¹

2015

Toxinology

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The inveterate botulinum neurotoxin A ushers in exo-endocytic crypts

Cited by 4 publications

References 21 publications

Capsaicin modulates acetylcholine release at the myoneural junction

Capsaicin modulates acetylcholine release at the myoneural junction

Biological Toxins and Bioterrorism

Antidotes to Botulinum Neurotoxin

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