TRANSIENT RECEPTOR POTENTIAL VANILLOID-1–MEDIATED CALCIUM RESPONSES ARE INHIBITED BY THE ALKYLAMINE ANTIHISTAMINES DEXBROMPHENIRAMINE AND CHLORPHENIRAMINE
- 1 January 2008
- journal article
- research article
- Published by Informa UK Limited in Experimental Lung Research
- Vol. 34 (10), 681-693
- https://doi.org/10.1080/01902140802339623
Abstract
American guidelines, unlike European guidelines, support the use of antihistamines as a first line of treatment for some causes of chronic cough. Transient receptor potential vanilloid-1 (TRPV1) is an ion channel activated by the tussive agents capsaicin, resiniferatoxin, and protons. It is predominantly expressed by C-fiber and some Aδ -fiber sensory neurons and is thought to be a cough receptor. By measuring increases in intracellular calcium as an indicator of TRPV1 activation, the authors sought to determine whether antihistamines could antagonise TRPV1 permanently expressed in HEK and Pro5 cells and TRPV1 endogenously expressed in rat dorsal root ganglia neurons. In human TRPV1–expressing HEK cells (hTRPV1-HEK), diphenhydramine and fexofenadine failed to inhibit capsaicin-triggered calcium responses. However, both dexbrompheniramine and chlorpheniramine significantly inhibited capsaicin-evoked responses in hTRPV1-HEK. Dexbrompheniramine also inhibited activation of rat TRPV1 expressed in HEK and Pro5 cells, without interfering with TRPA1 and proteinase-activated receptor-2 (PAR2) activation. Finally, in rat dorsal root ganglia neuron preparations, dexbrompheniramine dose-dependently inhibited capsaicin-evoked calcium responses. Thus, the inhibition of TRPV1 activation by dexbrompheniramine may provide one potential mechanism whereby this antihistamine exerts its therapeutic effect in chronic cough.Keywords
This publication has 29 references indexed in Scilit:
- TRPs in bladder diseasesBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2007
- Pharmacology and Antitussive Efficacy of 4-(3-Trifluoromethyl-pyridin-2-yl)-piperazine-1-carboxylic Acid (5-Trifluoromethyl-pyridin-2-yl)-amide (JNJ17203212), a Transient Receptor Potential Vanilloid 1 Antagonist in Guinea PigsJournal of Pharmacology and Experimental Therapeutics, 2007
- Characterization of SB-705498, a Potent and Selective Vanilloid Receptor-1 (VR1/TRPV1) Antagonist That Inhibits the Capsaicin-, Acid-, and Heat-Mediated Activation of the ReceptorJournal of Pharmacology and Experimental Therapeutics, 2007
- ERS guidelines on the assessment of coughEuropean Respiratory Journal, 2007
- Protease-activated receptor-2 activation exaggerates TRPV1-mediated cough in guinea pigsJournal of Applied Physiology, 2006
- Vanilloid receptor expressed in the sarcoplasmic reticulum of rat skeletal muscleBiochemical and Biophysical Research Communications, 2005
- 5-Iodoresiniferatoxin Evokes Hypothermia in Mice and Is a Partial Transient Receptor Potential Vanilloid 1 Agonist in VitroJournal of Pharmacology and Experimental Therapeutics, 2005
- TRPV1 and coughThorax, 2004
- Functional Vanilloid Receptors in Cultured Normal Human Epidermal KeratinocytesBiochemical and Biophysical Research Communications, 2002
- Immunoreactivity of VR1 on Epidermal Keratinocyte of Human SkinBiochemical and Biophysical Research Communications, 2001