Functional characterisation of tachykinin receptors in the circular muscle layer of the mouse ileum

Objectives: Tachykinins are important mediators in neuromuscular signalling but have not been thoroughly characterised in the mouse gut. We investigated the participation of tachykinin receptors in contractility of circular muscle strips of the mouse ileum. Results: Electrical field stimulation (EFS) of excitatory nonadrenergic noncholinergic (NANC) nerves induced frequency-dependent contractions which were mimicked by substance P (SP). Desensitisation of SP and NK1, NK2 or NK3 receptors significantly reduced contractions to EFS. The NK1 receptor blocker RP67580 significantly inhibited NANC contractions to EFS. The NK2 and NK3 receptor blockers nepadutant and SR142801 did not affect NANC contractions per se but increased the RP67580-induced inhibition of NANC contractions to EFS. Contractions to SP were significantly reduced by RP67580 but not affected by nepadutant or SR142801. The NK1 and NK2 receptor agonists, septide and [beta-ala(8)]-NKA 4-10 (beta-A-NKA), respectively, but not the NK3 receptor agonist senktide-induced dose-dependent contractions. Atropine inhibited and L-NNA augmented contractions to septide. Contractions to beta-A-NKA were insensitive to atropine but augmented by L-NNA. Conclusions: Tachykinins mediate NANC contractions to EFS in the mouse small intestine. Endogenously released tachykinins activate mainly NK1 receptors, located on cholinergic nerves and smooth muscle cells and, to a lesser degree, NK2 and NK3 receptors, most likely located presynaptically. (C) 2005 Elsevier B.V. All rights reserved.