Tachykinergic neurotransmission is enhanced in duodenum from dystrophic (mdx) mice.
1 Duodenal longitudinal muscle of mdx mice, an animal model for Duchenne muscular dystrophy, showed a decrease in the electrically evoked nonadrenergic, noncholinergic (NANC) inhibitory responses associated with a reduction of the participation of nitric oxide (NO). In this study, we investigated whether the impairment of NO could also lead to alterations in the NANC excitatory transmission. 2 Nerve-evoked responses consisted of an inhibitory phase followed, at the end of stimulation, by an excitatory response characterised by an increase in amplitude of the spontaneous contractions. In mdx mice, the amplitude of the nerve-evoked contractions was significantly higher than in normals. 3 N(omega)-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase, increased the amplitude of the nerve-evoked contractions only in normals, being ineffective in mdx mice. Apamin, a blocker of Ca(2+)-dependent potassium channels, failed to affect the nerve-evoked contractions. 4 In both models, substance P and neurokinin A produced concentration-dependent contractions, reduced by tachykinin NK(1) and NK(2) receptor antagonists, respectively. Moreover, NK(1) and NK(2) receptor antagonists reduced the amplitude of the nerve-evoked contractions. 5 Sodium nitroprusside (SNP) reduced the amplitude of nerve-evoked contractions similarly in normal and mdx mice. ODQ, but not apamin, prevented the SNP-induced effects. SNP did not affect the contractions induced by exogenous tachykinins. 6 The results suggest that NO can exert an inhibitory modulatory role on tachykinergic excitatory transmission via activation of guanylyl cyclase in mouse duodenum. In mdx mice, the impairment of NO function leads to an increase in the nerve-evoked contractions.
Zizzo
Maria Grazia
MG
Laboratorio di Fisiologia generale, Dipartimento di Medicina Sperimentale, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italia.
Mulè
Flavia
F
Serio
Rosa
R
D000818:Animals; D004386:Duodenum / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000503:physiopathology*; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015320:Tachykinins / Q000494:pharmacology / Q000502:physiology*
D018039:Receptors, Tachykinin; D015320:Tachykinins