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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Rigoni, Michela Trevisani, Marcello Geppetti, Pierangelo Gazzieri, David Davis, John B. Campi, Barbara Creminon, Christophe Nadaletto, Riccardo Amadesi, Silvia Harrison, Selena Tognetto, Michele |
| Description | Author Affiliation: Rigoni M ( Department of Experimental & Clinical Medicine, Pharmacology Unit, University of Ferrara, Via Fossato di Mortara 19, 44100 Ferrara, Italy.) |
| Abstract | (1) 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. (2) 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). (3) We have demonstrated that I-RTX inhibited capsaicin-induced mobilization of intracellular Ca(2+) in rat trigeminal neurons (IC(50) 0.87 nM) and in HEK293 cells transfected with the human TRPV1 (IC(50) 0.071 nM). (4) Furthermore, I-RTX significantly inhibited both capsaicin-induced CGRP release from slices of rat dorsal spinal cord (IC(50) 0.27 nM) 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. (5) Finally, in vivo I-RTX significantly inhibited acetic acid-induced writhing in mice (ED(50) 0.42 micro mol kg(-1)) and plasma extravasation in mouse urinary bladder (ED(50) 0.41 micro mol kg(-1)). (6) In in vitro and in vivo TRPV1 activated responses I-RTX was approximately 3 log units and approximately 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. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 5 |
| Volume Number | 138 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2003-03-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Diterpenes Pharmacology Neurons Drug Effects Pain Measurement Receptors, Drug Antagonists & Inhibitors Animals Cell Line Dose-Response Relationship, Drug Guinea Pigs Mice Muscle Contraction Physiology Metabolism Rats, Sprague-Dawley Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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