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RESEARCH PRODUCT

Altered tachykinergic influence on gastric mechanical activity in mdx mice

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Abstract This study investigated whether alterationsin gastric activity in dystrophic mdx mouse can beattributed to dysfunctions of tachykinins. Endolumi-nal pressure was recorded and the expression ofneuronal nitric oxide synthase (nNOS), NK1 and NK2neurokinin receptors was investigated by immunoh-istochemistry. SR48968, NK2 receptor antagonist, butnot SR140333, NK1 receptor antagonist, decreased thetone only in mdx gastric preparations. In the presenceof N x -nitro- L -arginine methyl ester ( L -NAME), inhib-itor of NOS, SR48968 reduced the tone also in normalstomach. [Sar 9 , Met(O 2 ) 11 ]-SP, agonist of NK1 recep-tors, caused tetrodotoxin-sensitive relaxations, antag-onized by SR140333 or L -NAME, with no difference inthe potency or efficacy between normal and mdxpreparations. [b-Ala 8 ]-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 demon-strated a 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 stom-ach the activation of NK2 receptors plays a role in thedevelopment of the tone, associated with a reducedNO production by muscular nNOS. The hypo-respon-siveness to NK2 receptors could depend on thereduced expression of these receptors.Keywords immunohistochemistry, mdx mouse, nitricoxide, stomach, tachykinins.