Transient receptor potential channels as novel drug targets in respiratory diseases.
A subpopulation of nociceptive primary sensory neurons expresses six different transient receptor potential (TRP) ion channels of the vanilloid (V1, V2, V3 and V4), melastatin (M8) and ankyrin (A1) subtypes. TRPV1 mediates the tussive action of capsaicin, which is widely used in cough provocation studies. The upregulation of TRPV1 expression and function has been reported in asthma and other inflammatory conditions. TRPA1 is targeted by a series of byproducts of oxidative and nitrative stress, including acrolein, 4-hydroxy-2-nonenal and hydrogen peroxide. Proinflammatory neuropeptides are released from nociceptive nerve terminals after TRPV1/TRPA1 stimulation, thereby causing airway neurogenic inflammation. In addition, the early inflammatory response to cigarette smoke is mediated entirely by neuronal TRPA1. TRPV1 and TRPA1 antagonists may therefore represent potential antitussive and anti-inflammatory therapeutics for respiratory airway diseases.
Nassini
Romina
R
University of Florence, Department of Preclinical and Clinical Pharmacology, Viale Pieraccini 6, 50139, Florence, Italy.
Materazzi
Serena
S
De Siena
Gaetano
G
De Cesaris
Francesco
F
Geppetti
Pierangelo
P
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D009479:Neuropeptides / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects* / Q000276:immunology / Q000294:innervation / Q000378:metabolism; D012140:Respiratory Tract Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D000893:Anti-Inflammatory Agents; D009479:Neuropeptides; D050051:Transient Receptor Potential Channels