Modulatory role of tachykinin NK1 receptor in cholinergic contraction of mouse trachea.
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.
Tournoy
K G
KG
Dept Respiratory Diseases, Ghent University Hospital, De Pintelaan, Ghent, Belgium.
De Swert
K O
KO
Leclere
P G
PG
Lefebvre
R A
RA
Pauwels
R A
RA
Joos
G F
GF
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
D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; C085215:SR 140333; D013373:Substance P; D013779:Tetrodotoxin; D001285:Atropine