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• W2022332945 startingPage "977" @default.
• W2022332945 abstract "Stimulation of the vanilloid receptor‐1 (TRPV1) results in the activation of nociceptive and neurogenic inflammatory responses. Poor specificity and potency of TRPV1 antagonists has, however, limited the clarification of the physiological role of TRPV1. Recently, iodo‐resiniferatoxin (I‐RTX) has been reported to bind as a high affinity antagonist at the native and heterologously expressed rat TRPV1. Here we have studied the ability of I‐RTX to block a series of TRPV1 mediated nociceptive and neurogenic inflammatory responses in different species (including transfected human TRPV1). We have demonstrated that I‐RTX inhibited capsaicin‐induced mobilization of intracellular Ca 2+ in rat trigeminal neurons (IC 50 0.87 n M ) and in HEK293 cells transfected with the human TRPV1 (IC 50 0.071 n M ). Furthermore, I‐RTX significantly inhibited both capsaicin‐induced CGRP release from slices of rat dorsal spinal cord (IC 50 0.27 n M ) and contraction of isolated guinea‐pig and rat urinary bladder (pK B of 10.68 and 9.63, respectively), whilst I‐RTX failed to alter the response to high KCl or SP. Finally, in vivo I‐RTX significantly inhibited acetic acid‐induced writhing in mice (ED 50 0.42 μmol kg −1 ) and plasma extravasation in mouse urinary bladder (ED 50 0.41 μmol kg −1 ). In in vitro and in vivo TRPV1 activated responses I‐RTX was ∼3 log units and ∼20 times more potent than capsazepine, respectively. This high affinity antagonist, I‐RTX, may be an important tool for future studies in pain and neurogenic inflammatory models. British Journal of Pharmacology (2003) 138 , 977–985. doi: 10.1038/sj.bjp.0705110" @default.
• W2022332945 created "2016-06-24" @default.
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• W2022332945 date "2003-03-01" @default.
• W2022332945 modified "2023-10-15" @default.
• W2022332945 title "Neurogenic responses mediated by vanilloid receptor-1 (TRPV1) are blocked by the high affinity antagonist, iodo-resiniferatoxin" @default.
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• W2022332945 doi "https://doi.org/10.1038/sj.bjp.0705110" @default.
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