Mechanical responses evoked by nerve stimulation in gastric muscles of mouse lacking inositol trisphosphate receptor

Alteration of mechanical responses elicited by transmural nerve stimulation (TNS) was investigated in pylorus muscle of stomach isolated from mutant m ice lacking expression of IP3 type-1 receptor. In wild and mutant mice, TNS inhibited spontaneous contractions and generated an off-response at the ce ssation. The effects of inhibitors of neurotransmission revealed that in wi ld mice, acetylcholine and nitric oxide were involved as excitatory and inh ibitory mediators, respectively. In mutant mice, a lack of nitroxidergic co mponent with associated attenuation of cholinergic transmission was found. The off-response was inhibited by apamin in both mice. In mutant mice, span tide-sensitive excitatory response appeared in the presence of apamin. Acet ylcholine and substance P enhanced while noradrenaline and sodium nitroprus side inhibited spontaneous contractions, in both wild and mutant mice; the actions were weaker in mutant mice than in wild mice for any agonists. The results indicate that pylorus smooth muscles receive cholinergic excitatory and nitroxidergic and non-adrenergic non-cholinergic inhibitory projection s, and a lack of IP3 type-1 receptor results in an impairment of cholinergi c and nitroxidergic components, with no alteration of non-adrenergic non-ch olinergic inhibitory projections. In addition, the mutation induces a subst ance P projection which is not detected in wild mice. (C) 2001 Elsevier Sci ence B.V. All rights reserved.