title: Transient receptor potential vanilloid-1-mediated calcium responses are inhibited by the alkylamine antihistamines dexbrompheniramine and chlorpheniramine.
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 Adelta -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 (PAR(2)) 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.
authors.affiliation: Division of Cardiovascular and Respiratory Studies, Hull York Medical School, University of Hull, Castle Hill Hospital, Cottingham, United Kingdom. A.H.Morice@hull.ac.uk
authors.forename: Laura R
authors.initials: LR
authors.lastname: Sadofsky
authors.forename: Barbara
authors.initials: B
authors.lastname: Campi
authors.forename: Marcello
authors.initials: M
authors.lastname: Trevisani
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Compton
authors.forename: Alyn H
authors.initials: AH
authors.lastname: Morice
mesh_terms: D000818:Animals; D001977:Brompheniramine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D002211:Capsaicin / Q000494:pharmacology; D002460:Cell Line; D002744:Chlorpheniramine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors
chemical_list: D015220:Calcium Channels; D006633:Histamine Antagonists; D009419:Nerve Tissue Proteins; D044464:Receptor, PAR-2; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D050051:Transient Receptor Potential Channels; D002744:Chlorpheniramine; C015121:dexbrompheniramine; D001977:Brompheniramine; D002211:Capsaicin; D002118:Calcium