Dickson Eamonn J, Spencer Nick J, Hennig Grant W, Bayguinov Peter O, Ren Jim, Heredia Dante J, Smith Terence K
Department of Physiology & Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA.
Gastroenterology. 2007 May;132(5):1912-24. doi: 10.1053/j.gastro.2007.02.047. Epub 2007 Feb 23.
BACKGROUND & AIMS: Transit of fecal material through the human colon takes > or =30 hours, whereas transit through the small intestine takes 24 hours. The mechanisms underlying colonic storage and slow transit have yet to be elucidated. Our aim was to determine whether an intrinsic neural mechanism underlies these phenomena.
Recordings were made from circular muscle (CM) cells and myenteric neurons in the isolated guinea pig distal colon using intracellular recordings and Ca(2+) imaging techniques. Video imaging was used to determine the effects of colonic filling and pellet transit.
Circumferential stretch generated ongoing oral excitatory and anal inhibitory junction potentials in the CM. The application of longitudinal stretch inhibited all junction potentials. N-omega-nitro-L-arginine (100 micromol/L) completely reversed the inhibitory effects of longitudinal stretch suggesting that nitric oxide (NO) inhibited interneurons controlling peristaltic circuits. Ca(2+) imaging in preparations that were stretched in both axes revealed ongoing firing in nNOS +ve descending neurons, even when synaptic transmission was blocked. Inhibitory postsynaptic potentials were evoked in mechanosensitive interneurons that were blocked by N-omega-nitro-L-arginine (100 micromol/L). Pellet transit was inhibited by longitudinal stretch. Filling the colon with fluid led to colonic elongation and an inhibition of motility.
Our data support the novel hypothesis that slow transit and accommodation are generated by release of NO from descending (nNOS +ve) interneurons triggered by colonic elongation. We refer to this powerful inhibitory reflex as the intrinsic occult reflex (hidden from observation) because it withdraws motor activity from the muscle.
粪便物质通过人体结肠的传输时间≥30小时，而通过小肠的传输时间为24小时。结肠储存和传输缓慢的机制尚待阐明。我们的目的是确定这些现象是否由内在神经机制引起。
使用细胞内记录和Ca(2+)成像技术，对分离的豚鼠远端结肠的环形肌（CM）细胞和肌间神经进行记录。采用视频成像来确定结肠充盈和粪便传输的影响。
周向拉伸在CM中产生持续的口侧兴奋性和肛侧抑制性连接电位。纵向拉伸的应用抑制了所有连接电位。N-ω-硝基-L-精氨酸（100 μmol/L）完全逆转了纵向拉伸的抑制作用，表明一氧化氮（NO）抑制了控制蠕动回路的中间神经元。在双轴拉伸的制剂中进行Ca(2+)成像显示，即使突触传递被阻断，nNOS阳性下行神经元仍持续放电。在机械敏感的中间神经元中诱发了抑制性突触后电位，该电位被N-ω-硝基-L-精氨酸（100 μmol/L）阻断。纵向拉伸抑制了粪便传输。向结肠内注入液体导致结肠伸长并抑制了蠕动。
我们的数据支持了一个新的假说，即结肠伸长触发下行（nNOS阳性）中间神经元释放NO，从而产生传输缓慢和适应性变化。我们将这种强大的抑制性反射称为内在隐匿反射（难以观察到），因为它使肌肉的运动活动减弱。
