Taurolidine and congeners activate hTRPA1 but not hTRPV1 channels and stimulate CGRP release from mouse tracheal sensory nerves
Kichko T, Pfirrmann RW, Reeh P (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 4
Journal Issue: 1
DOI: 10.1002/prp2.204
Abstract
Taurolidine has long been in clinical use as an antimicrobial irrigation that does not impede wound healing. It can even be administered intravenously (30 g/day) to treat sepsis or to exert newly recognized antineoplastic actions. Only one irritant effect is reported, that is, to temporarily induce burning pain of unknown origin when applied to body cavities or peripheral veins. The structure of the molecule suggested the chemoreceptor channel TRPA1 as a potential target, which was verified measuring stimulated CGRP release from sensory nerves of the isolated mouse trachea and calcium influx in hTRPA1-transfected HEK293 cells. With both methods, the concentration-response relationship of taurolidine exceeded the threshold value below 500 μmol/L and 100 μmol/L, respectively, and reached saturation at 1 mmol/L. The clinical 2% taurolidine solution did not evoke greater or longer lasting responses. The reversible tracheal response was abolished in TRPA1(-/-) but retained in TRPV1(-/-) mice. Consistently, hTRPV1-HEK showed no calcium influx as a response, likewise native HEK293 cells and hTRPA1-HEK deprived of extracellular calcium did not respond to taurolidine 1 mmol/L. The metabolite taurultam and its oxathiazine derivative, expected to cause less burning pain, showed weak tracheal irritancy only at 10 mmol/L, acting also through hTRPA1 but not hTRPV1. In conclusion, taurolidine, its metabolite, and a novel derivative showed no unspecific cellular effects but selectively, concentration-dependently and reversibly activated the irritant receptor TRPA1 in CGRP-expressing, thus nociceptive, neurons. The clinical solution of 2% taurolidine (~70 mmol/L) can, thus, rightly be expected to cause transient burning pain and neurogenic inflammation.
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Switzerland (CH)How to cite
APA:
Kichko, T., Pfirrmann, R.W., & Reeh, P. (2016). Taurolidine and congeners activate hTRPA1 but not hTRPV1 channels and stimulate CGRP release from mouse tracheal sensory nerves. Pharmacology Research and Perspectives, 4(1). https://doi.org/10.1002/prp2.204
MLA:
Kichko, Tetyana, Rolf W. Pfirrmann, and Peter Reeh. "Taurolidine and congeners activate hTRPA1 but not hTRPV1 channels and stimulate CGRP release from mouse tracheal sensory nerves." Pharmacology Research and Perspectives 4.1 (2016).
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