Role for NK1 and NK2 receptors in the motor activity in mouse colon.

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The present study examined the effects induced by endogenous and exogenous activation of NK1 and NK2 receptors on the mechanical activityof mouse proximal colon. Experiments were performed in vitro recording the changes in intraluminal pressure from isolated colonic segments.Electrical field stimulation in the presence of atropine and guanethidine produced a small relaxation, followed by nonadrenergic noncholinergic(NANC) contraction. SR140333, NK1 receptor antagonist, or SR48968, NK2 receptor antagonist, significantly reduced the contraction, althoughSR48968 appeared more efficacious. The co-administration of SR140333 and SR48968 virtually abolished the NANC contraction. [Sar9, Met(O2)11]-substance P, selective NK1 receptor agonist, induced a concentration-dependent biphasic effect, contraction followed by reduction of themechanical spontaneous activity. Both effects were antagonized by SR140333, but not by SR48968. [β-Ala8]-neurokinin A (4-10), selective NK2receptor agonist, evoked concentration-dependent contraction, which was antagonized by SR48968, but not by SR140333. The contractioninduced by [Sar9, Met(O2)11]-substance P, but not by [β-Ala8]-neurokinin A (4-10), was reduced by tetrodotoxin or atropine, and increased by Nω-nitro-L-arginine methyl ester (L-NAME), inhibitor of nitric oxide synthase. The inhibitory effects induced by [Sar9, Met(O2)11]-substance P wereabolished by tetrodotoxin or L-NAME. The results of the present study suggest that in mouse colon both NK1 and NK2 receptors are junctionallyactivated by endogenous tachykinins to cause an additive response. NK1 receptors appear to be located on cholinergic and on nitrergic neurons aswell as on smooth muscle cells, whereas NK2 receptors seem to be present exclusively on smooth muscle cells.
Lingua originaleEnglish
pagine (da-a)196-202
Numero di pagine7
RivistaEuropean Journal of Pharmacology
Stato di pubblicazionePublished - 2007

All Science Journal Classification (ASJC) codes

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