Garella Rachele, Baccari Maria Caterina
Department of Physiological Sciences, University of Florence, I-50134 Florence, Italy.
Regul Pept. 2010 Feb 25;160(1-3):57-63. doi: 10.1016/j.regpep.2009.12.012. Epub 2009 Dec 24.
Gastrointestinal motor disorders have been reported to occur in dystrophic (mdx) mice. The aim of the present study was to investigate the contribution of endogenous nitrergic and peptidergic components to the gastric contractile responses in strips from wild type (WT) and mdx mice. In both preparations, electrical field stimulation (EFS) induced frequency-dependent excitatory responses that were abolished by atropine or tetrodotoxin. The amplitude of the neurally-induced contractile responses was greater in strips from mdx mice in respect to the WT ones. In both preparations, at the end of the stimulation period strip tension decayed below the pre-stimulus level (off-relaxations). The nitric oxide (NO) synthesis inhibitor L-NNA increased the amplitude of the EFS-induced contractile responses without influencing off-relaxations. alpha-chymotrypsin and PACAP 6-38 abolished off-relaxations and also caused a reduction in amplitude of the contractile responses, whereas VIP receptor antagonists were ineffective. The efficacy of L-NNA, alpha-chymotrypsin or PACAP 6-38 on the excitatory responses was lower in strips from mdx mice in respect to the WT ones. alpha-chymotrypsin, in the presence of L-NNA, was no longer able to decrease the amplitude of the neurally-induced contractile responses but still abolished off-relaxations in both preparations. Direct muscular responses to methacholine were similar in amplitude in the two preparations and were not influenced by L-NNA or alpha-chymotrypsin. The results indicate that both endogenous NO and peptides influence the EFS-induced cholinergic responses: a stronger peptidergic modulatory action on a weaker nitrergic neurotransmission is suggested to occur in strips from mdx mice in respect to the WT ones and to contribute to the altered gastric contractile responses.
据报道，营养不良（mdx）小鼠会出现胃肠运动障碍。本研究的目的是调查内源性一氧化氮能和肽能成分对野生型（WT）和mdx小鼠胃条收缩反应的作用。在两种制剂中，电场刺激（EFS）均诱导出频率依赖性兴奋反应，这些反应可被阿托品或河豚毒素消除。与WT小鼠相比，mdx小鼠胃条中神经诱导的收缩反应幅度更大。在两种制剂中，刺激期结束时，胃条张力衰减至刺激前水平以下（脱逸性舒张）。一氧化氮（NO）合成抑制剂L-NNA增加了EFS诱导的收缩反应幅度，而不影响脱逸性舒张。α-糜蛋白酶和PACAP 6-38消除了脱逸性舒张，还导致收缩反应幅度降低，而VIP受体拮抗剂无效。与WT小鼠相比，L-NNA、α-糜蛋白酶或PACAP 6-38对mdx小鼠胃条兴奋反应的作用效力较低。在L-NNA存在的情况下，α-糜蛋白酶不再能够降低神经诱导的收缩反应幅度，但仍能消除两种制剂中的脱逸性舒张。两种制剂中对乙酰甲胆碱的直接肌肉反应幅度相似，且不受L-NNA或α-糜蛋白酶的影响。结果表明，内源性NO和肽均影响EFS诱导的胆碱能反应：与WT小鼠相比，mdx小鼠胃条中肽能对较弱的一氧化氮能神经传递的调节作用更强，这可能导致胃收缩反应改变。
