title: Capsaicin and neurokinin A-induced bronchoconstriction in the anaesthetised guinea-pig: evidence for a direct action of menthol on isolated bronchial smooth muscle.
abstract: 1. For many years menthol has been used in the treatment of respiratory disorders although, a bronchodilator effect of menthol has yet to be described. Using the bronchoconstrictors capsaicin (acting via stimulating the release of neuropeptides from sensory afferents) and neurokinin A (NKA) we have raised airways resistance in the guinea-pig (GP) and studied the effect of menthol on both capsaicin and NKA-induced bronchoconstriction in vivo. In vitro the effect of menthol on acetylcholine (ACh) and KCl precontracted GP bronchi was also studied. 2. GP (n = 13) were anaesthetized (urethane 1.5 g kg-1, i.p.) and a bolus injection of capsaicin (7.5 micrograms ml-1, i.v.) or infusion of NKA (1 microgram min-1, i.v.) was given either in the presence of air (0.81 min-1) or air impregnated with menthol vapour (7.5 micrograms l-1) freely breathed from a tracheal cannula via a T-piece. Airways resistance (Raw) and ventilation were measured throughout. Bronchi of mean internal diameter (1029 + 73.6 microns; n = 24) were removed from GP (n = 16) and mounted in the Cambustion myograph. Bronchial rings were maximally precontracted with 80 mM KCl or 2 mM ACh. Relaxation due to a cumulative dose of menthol (1- 3000 microM) was measured. 3. Menthol produced a significant (P < 0.05) 51.3% reversal of the capsaicin-induced increase in Raw, and also inhibited the significant (P < 0.05) reduction in minute ventilation (Ve) associated with the capsaicin-induced increased in Raw. Menthol also caused a significant (P < 0.05) 41% reversal of the NKA-induced increase in Raw. The NKA-induced decrease in Ve was again significantly (P < 0.05) reversed with menthol inhalation. Menthol caused a significant (P < 0.001) dose-dependent relaxation of KCl and ACh precontracted bronchi. 4. We have shown that menthol attenuates both capsaicin and NKA-induced bronchoconstriction in vivo and relaxes KCl and ACh preconstricted bronchi in vitro. Menthol inhibition of NKA and capsaicin-induced bronchoconstriction could be, in part, explained by a direct action of menthol on bronchial smooth muscle.
authors.affiliation: Department of Medicine and Pharmacology, University of Sheffield.
authors.forename: C E
authors.initials: CE
authors.lastname: Wright
authors.forename: E A
authors.initials: EA
authors.lastname: Laude
authors.forename: T J
authors.initials: TJ
authors.lastname: Grattan
authors.forename: A H
authors.initials: AH
authors.lastname: Morice
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000758:Anesthesia; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D016084:Bronchoconstriction / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008610:Menthol / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D015288:Neurokinin A / Q000494:pharmacology*
chemical_list: D008610:Menthol; D015288:Neurokinin A; D002211:Capsaicin; D002118:Calcium