Altered tachykinergic influence on gastric mechanical activity in mdx mice

This study investigated whether alterationsin gastric activity in dystrophic mdx mouse can beattributed to dysfunctions of tachykinins. Endoluminalpressure was recorded and the expression ofneuronal nitric oxide synthase (nNOS), NK1 and NK2neurokinin receptors was investigated by immunohistochemistry.SR48968, NK2 receptor antagonist, butnot SR140333, NK1 receptor antagonist, decreased thetone only in mdx gastric preparations. In the presenceof Nx-nitro-L-arginine methyl ester (L-NAME), inhibitorof NOS, SR48968 reduced the tone also in normalstomach. [Sar9, Met(O2)11]-SP, agonist of NK1 receptors,caused tetrodotoxin-sensitive relaxations, antagonizedby SR140333 or L-NAME, with no difference inthe potency or efficacy between normal and mdxpreparations. [b-Ala8]-NKA(4-10), an NK2 receptoragonist, induced SR48968-sensitive contractions inboth types of preparations, although the maximalresponse of mdx tissues was significantly lower thannormal preparations. Immunohistochemistry demonstrateda consistent reduction of nNOS and NK2receptor expression in mdx stomach smooth musclecells and no change in nNOS and NK1 receptorexpression in neurones. In conclusion, in mdx stomachthe activation of NK2 receptors plays a role in thedevelopment of the tone, associated with a reducedNO production by muscular nNOS. The hypo-responsivenessto NK2 receptors could depend on thereduced expression of these receptors.