Capsazepine is known as a transient receptor potential channel vanilloid subfamily 1 (TRPV1) antagonist that inhibits bronchoconstriction evoked in animals by TRPV1 agonists. In this study, effects of capsazepine and chemically related analogues, so called capsazepinoids, were examined in vitro on contractile effects in human small airway preparations. Repeated cycles with 1 h of LTD4-free physiological saline solution followed by 30 min exposure to LTD4 (10 nM) demonstrated that the contractile responsiveness of the preparations exhibited little change over time despite repeated challenges (> 12 h). Capsazepine (1-100 mu M) reversibly and concentration-dependently inhibited the contractile response to LTD4 with EC50 similar to 10 mu M and similar to 90% relaxation at 100 mu M. Capsazepine (10 M) was approximately equally effective to attenuate the contractions evoked by several different inflammatory contractile agonists (LTD4, PGD(2), histamine), and it relaxed preparations with established tonic contraction due to LTD4. Higher concentrations of capsazepine were needed to relax ACh-contractions. The effect of capsazepine on LTD4-induced contractions was not significantly reduced by pre-treating the preparations with either of propranotol (10 mu M) + atropine (1 mu M), L-NAME (1 mM), indomethacin (1 mu M), iberiotoxin (0.1 mu M), capsaicin (10 mu M), and nifedipine (10 mu M). Although the mechanism of action of the present capsazepine-induced bronchorelaxation remains unknown it emerged here that they represent a generally effective principle exerting a functional antagonism against contractile mediators but distinct from beta receptor agonists and inhibitors of L-type calcium channels. The inhibitory effect of capsazepine is shared by chemical analogues, but not with other TRPV1 antagonists, suggesting the possibility that capsazepine represents a novel class of bronchorelaxants effective in human small airways. These findings were not predicted by previous observations that have concerned quite limited effects of capsazepine on airway tone in different animal test systems. If potency can be further increased and the results translated to in vivo, compounds representing the capsazepinoid class of bronchorelaxants might become useful in the treatment of patients suffering from asthma and COPD.
Bibliographical noteThe information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240), Division of Clinical Chemistry and Pharmacology (013250300), Thoracic Surgery (013230027)
Subject classification (UKÄ)
- Medicinal Chemistry
- Pharmacology and Toxicology
- Cardiac and Cardiovascular Systems
- capsazepine bronchorelaxant
- small airways