De Schepper Heiko U, De Winter Benedicte Y, Seerden Tom C, Herman Arnold G, Pelckmans Paul A, De Man Joris G
Division of Gastroenterology, Faculty of Medicine, University of Antwerp, Universiteitsplein 1, Wilrijk B-2610, Belgium.
Regul Pept. 2005 Sep 15;130(3):105-15. doi: 10.1016/j.regpep.2005.04.003.
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.
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 NK(1), NK(2) or NK(3) receptors significantly reduced contractions to EFS. The NK(1) receptor blocker RP67580 significantly inhibited NANC contractions to EFS. The NK(2) and NK(3) 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 NK(1) and NK(2) receptor agonists, septide and [beta-ala(8)]-NKA 4-10 (beta-A-NKA), respectively, but not the NK(3) 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.
Tachykinins mediate NANC contractions to EFS in the mouse small intestine. Endogenously released tachykinins activate mainly NK(1) receptors, located on cholinergic nerves and smooth muscle cells and, to a lesser degree, NK(2) and NK(3) receptors, most likely located presynaptically.
速激肽是神经肌肉信号传导中的重要介质，但在小鼠肠道中尚未得到充分表征。我们研究了速激肽受体在小鼠回肠环形肌条收缩中的作用。
对兴奋性非肾上腺素能非胆碱能（NANC）神经进行电场刺激（EFS）可诱导频率依赖性收缩，P物质（SP）可模拟这种收缩。SP以及NK(1)、NK(2)或NK(3)受体脱敏显著降低了对EFS的收缩反应。NK(1)受体阻滞剂RP67580显著抑制了NANC对EFS的收缩。NK(2)和NK(3)受体阻滞剂奈帕肽和SR142801本身并不影响NANC收缩，但增强了RP67580对NANC收缩至EFS的抑制作用。RP67580显著降低了对SP的收缩反应，但奈帕肽或SR142801对其无影响。NK(1)和NK(2)受体激动剂，即九肽和[β-丙氨酸(8)]-神经激肽A 4-10（β-A-NKA），分别可诱导剂量依赖性收缩，但NK(3)受体激动剂速激肽无此作用。阿托品抑制了对九肽的收缩，而L-硝基精氨酸（L-NNA）增强了这种收缩。对β-A-NKA的收缩对阿托品不敏感，但L-NNA可增强这种收缩。
速激肽介导小鼠小肠中NANC对EFS的收缩。内源性释放的速激肽主要激活位于胆碱能神经和平滑肌细胞上的NK(1)受体，在较小程度上激活最可能位于突触前的NK(2)和NK(3)受体。
