title: Modulatory role of tachykinin NK1 receptor in cholinergic contraction of mouse trachea.
abstract: The role of the NK1 receptor in airway contraction induced by electrical field stimulation (EFS) was evaluated by comparing the response in NK1 receptor knockout mice (NK1R-/-) with that of NK1 receptor wild-type controls (WT). A frequency/response curve on tracheas from NK1R-/- mice and NK1R WT littermates was constructed. After incubation with [3H]choline, [3H]acetylcholine release upon EFS was measured by high-performance liquid chromatography and liquid scintillation counting. The effects of atropine (1 x 10(-6) M), tetrodotoxin (1 x 10(-6) M) and a specific NK1R antagonist (SR140333, 1 x 10(-8) M) were studied, as well as the effects of substance P (1 x 10(-5) M) on precontracted tracheas. Upon EFS, NK1R-/- mice had a significant lower trachea contractility than the NK1R WT animals, accompanied with less [3H]acetylcholine release. Pretreatment with atropine or tetrodotoxin abolished the EFS-induced contraction in both strains. Pretreatment with the NK1R antagonist SR140333 significantly reduced the contractility in the NK1R WT but not in the NK1R-/- mice. Substance P caused a small contraction in both NK1R WT and NK1R-/- mice. Substance P induced a relaxation in precontracted tracheas in NK1R WT but not in NK1R-/- mice. The data presented here provide direct evidence that the NK1 receptor augments cholinergic neurotransmission in mouse trachea.
authors.affiliation: Dept Respiratory Diseases, Ghent University Hospital, De Pintelaan, Ghent, Belgium.
authors.forename: K G
authors.initials: KG
authors.lastname: Tournoy
authors.forename: K O
authors.initials: KO
authors.lastname: De Swert
authors.forename: P G
authors.initials: PG
authors.lastname: Leclere
authors.forename: R A
authors.initials: RA
authors.lastname: Lefebvre
authors.forename: R A
authors.initials: RA
authors.lastname: Pauwels
authors.forename: G F
authors.initials: GF
authors.lastname: Joos
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004558:Electric Stimulation; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D013237:Stereoisomerism; D013373:Substance P / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014132:Trachea / Q000294:innervation* / Q000502:physiology
chemical_list: D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; C085215:SR 140333; D013373:Substance P; D013779:Tetrodotoxin; D001285:Atropine