Altered tachykinergic influence on gastric mechanical activity in mdx mice.
This study investigated whether alterations in gastric activity in dystrophic mdx mouse can be attributed to dysfunctions of tachykinins. Endoluminal pressure was recorded and the expression of neuronal nitric oxide synthase (nNOS), NK1 and NK2 neurokinin receptors was investigated by immunohistochemistry. SR48968, NK2 receptor antagonist, but not SR140333, NK1 receptor antagonist, decreased the tone only in mdx gastric preparations. In the presence of N(omega)-nitro-l-arginine methyl ester (l-NAME), inhibitor of NOS, SR48968 reduced the tone also in normal stomach. [Sar(9), Met(O(2))(11)]-SP, agonist of NK1 receptors, caused tetrodotoxin-sensitive relaxations, antagonized by SR140333 or l-NAME, with no difference in the potency or efficacy between normal and mdx preparations. [beta-Ala(8)]-NKA(4-10), an NK2 receptor agonist, induced SR48968-sensitive contractions in both types of preparations, although the maximal response of mdx tissues was significantly lower than normal preparations. Immunohistochemistry demonstrated a consistent reduction of nNOS and NK2 receptor expression in mdx stomach smooth muscle cells and no change in nNOS and NK1 receptor expression in neurones. In conclusion, in mdx stomach the activation of NK2 receptors plays a role in the development of the tone, associated with a reduced NO production by muscular nNOS. The hypo-responsiveness to NK2 receptors could depend on the reduced expression of these receptors.
Mulè
F
F
Dipartimento di Biologia Cellulare e dello Sviluppo, Laboratorio di Fisiologia generale, Università di Palermo, Palermo, Italy. fmule@unipa.it
Amato
A
A
Vannucchi
M G
MG
Faussone-Pellegrini
M S
MS
Serio
R
R
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D008365:Manometry; D051379:Mice; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000150:complications / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis; D009924:Organ Culture Techniques; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013270:Stomach / Q000187:drug effects / Q000503:physiopathology*; D015320:Tachykinins / Q000378:metabolism*
D001549:Benzamides; D004791:Enzyme Inhibitors; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; C085215:SR 140333; C073839:SR 48968; D052248:Nitric Oxide Synthase Type I; D019331:NG-Nitroarginine Methyl Ester