[Effects of tachykinin receptor antagonists on allergic asthma in guinea pigs].
In conscious sensitized guinea pigs, CP-96345 (2.06 mumol.kg-1, i.p.), a specific antagonist for tachykinin NK-1 receptors, SR-48968 (1.66 mumol.kg-1, i.p.), an NK-2 receptor antagonist, and the combination of both agents decreased the wheezing percentage and the mortality from anaphylactic shock induced by 0.25% ovalbumin (OA, for 0.5 or 2 min) aerosol inhalation. In the anesthetized guinea pigs, SR-48968 attenuated OA (5 mg.kg-1, i.v.)-induced bronchoconstriction, while CP-96345 inhibited OA-induced Evans blue extravasation in bronchi and intrapulmonary airways. In the isolated tracheal and bronchial smooth muscle preparations of guinea pigs, SR-48968 concentration-dependently inhibited OA (10 micrograms.ml-1)-induced contraction both in trachea and in bronchi, while CP-96345 only attenuated the contraction of bronchi. Pretreatment with capsaicin, a depleting agent of sensory neuropeptides from sensory nerve C-fibers, attenuated the OA-induced contractions both in trachea and in bronchi. The results indicate that (1) tachykinins in the airways are involved in the pathogenesis of allergic asthma; (2) tachykinin receptor antagonists have inhibitory effects on the allergic asthmatic responses, which is at least partly through the inhibition of antigen-induced contraction of airway smooth muscles (NK-2 receptor effect) and airway microvascular leakage (NK-1 receptor effect).
Zhang
W P
WP
Department of Pharmacology and Laboratory of Neurobiology, Zhejiang Medical University, Hangzhou 310031.
Lu
Z Y
ZY
Wei
E Q
EQ
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000503:physiopathology*; D001549:Benzamides / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D064729:Neurokinin-1 Receptor Antagonists; D010047:Ovalbumin; D010880:Piperidines / Q000494:pharmacology*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000187:drug effects
D001549:Benzamides; D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018041:Receptors, Neurokinin-2; D018039:Receptors, Tachykinin; C073839:SR 48968; D010047:Ovalbumin; C066892:CP 96345