Role of NK1and NK2receptors in mouse gastric mechanical activity

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Abstract
The aim of the present study was to examine the role of NK1and NK2receptors in the control of mechanical activity of mouse stomach. In this view, the motor effects induced by NK1and NK2receptor agonists and antagonists were analyzed, measuring motility as intraluminal pressure changes in mouse‐isolated stomach preparations. In parallel, immunohistochemical studies were performed to identify the location of NK1and NK2receptors on myenteric neurons and smooth muscle cells. Substance P (SP) induced biphasic effects: a contraction followed by relaxation; neurokinin A (NKA) and [β‐Ala8]‐NKA(4−10), selective agonist of NK2receptors, evoked concentration‐dependent contractions, whereas [Sar9, Met(O2)11]‐SP, selective agonist of NK1receptors, induced concentration‐dependent relaxation. SR48968, NK2receptor antagonist, did not modify the spontaneous activity and reduced the contractile effects induced by tachykinins without affecting the relaxation. SR140333, NK1receptor antagonist, did not modify the spontaneous activity and antagonized the relaxant response to tachykinins, failing to affect the contractile effects. The relaxation to SP or to [Sar9, Met(O2)11]‐SP was abolished by tetrodotoxin (TTX) and significantly reduced byN‐nitro‐L‐arginine methyl ester (L‐NAME). NK2‐immunoreactivity (NK2‐IR) was seen at the level of the smooth muscle cells of both circular and longitudinal muscle layers. NK1‐immunoreactive (NK1‐IR) neurons were seen in the myenteric ganglia and NK1/nNOS double labeling revealed that some neurons were both NK1‐IR and nNOS‐IR. These results suggest that, in mouse stomach, NK1receptors, causing relaxant responses, are present on nitrergic inhibitory myenteric neurons, whereas NK2receptors, mediating contractile responses, are present at muscular level. British Journal of Pharmacology(2006)147, 430–436. doi:10.1038/sj.bjp.0706645