Effect of SR-140333, a neurokinin-1 receptor antagonist, on airway reactivity to methacholine in sedated rats
Abstract
AIM: To study the roles of neurokinins in the airway reactivity (AR) to
methacholine chloride (MC).
METHODS: The effects of (S)-1-(2-[3,
4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)
piperidin-3-yl]ethyl)-4-phenyl-1-azoniabicyclo [2.2.2]octane.chloride
(SR-140333), a neurokinin-1 receptor antagonist, on AR to inhaled MC in
diazepam-sedated rats, and on MC-induced contraction of isolated tracheal spiral
strips were observed.
RESULTS: SR-140333 inhibited the increase in respiratory rate (RR) induced by MC
aerosol (10-1000 mumol/m3), and the ID50 for inhibiting the response to MC
aerosol (1 mmol/m3) was 4.9 micrograms.kg-1 (95% confidence limits 1.4-17.2
micrograms.kg-1). SR-140333 1 mumol.L-1 had no inhibitory effect on MC-induced
tracheal contraction. Atropine blocked responses to MC both in vivo and in vitro.
CONCLUSION: Endogenous neurokinins are involved in the AR to MC in rats, at least
partly mediated via neurokinin-1 receptors.
Keywords:
methacholine chloride (MC).
METHODS: The effects of (S)-1-(2-[3,
4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)
piperidin-3-yl]ethyl)-4-phenyl-1-azoniabicyclo [2.2.2]octane.chloride
(SR-140333), a neurokinin-1 receptor antagonist, on AR to inhaled MC in
diazepam-sedated rats, and on MC-induced contraction of isolated tracheal spiral
strips were observed.
RESULTS: SR-140333 inhibited the increase in respiratory rate (RR) induced by MC
aerosol (10-1000 mumol/m3), and the ID50 for inhibiting the response to MC
aerosol (1 mmol/m3) was 4.9 micrograms.kg-1 (95% confidence limits 1.4-17.2
micrograms.kg-1). SR-140333 1 mumol.L-1 had no inhibitory effect on MC-induced
tracheal contraction. Atropine blocked responses to MC both in vivo and in vitro.
CONCLUSION: Endogenous neurokinins are involved in the AR to MC in rats, at least
partly mediated via neurokinin-1 receptors.