Leelakusolvong S, Bharucha A E, Sarr M G, Hammond P I, Brimijoin S, Phillips S F
Gastroenterology Research Unit and Enteric Neurosciences Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
Neurogastroenterol Motil. 2003 Apr;15(2):173-86. doi: 10.1046/j.1365-2982.2003.00399.x.
To explore the hypothesis that denervation hypersensitivity increases ileocolonic motor activity after extrinsic denervation, we compared muscarinic neurotransmission in canine ileocolonic loops that were isolated and either extrinsically innervated or extrinsically denervated. We recorded ileal, ileocolonic sphincter (ICS) and colonic pressures, and colonic tone, compliance and relaxation during ileal distention. Muscarinic effects were probed by neostigmine, and minimally effective doses of muscarinic receptor antagonists. Denervation augmented ileal, ICS and colonic contractile activity; colonic high-amplitude propagating contractions (HAPCs) were also augmented; colonic relaxation during ileal distention was abolished. Neostigmine induced HAPCs in both loop preparations. Pirenzipine (M1 antagonist) reduced ileal contractile activity in all loops and reduced colonic relaxation during ileal distention in innervated loops. Pirenzipine also reduced colonic tone and colonic HAPCs, more in denervated loops. Darifenacin (M3 antagonist) reduced ileocolonic contractile activity and tone more than did AF-DX 116 (M2 antagonist) in all loops. Cholinergic receptor subtypes modulate different facets of ileocolonic motor activity in the canine ileocolonic region. Increased sensitivity at M1 muscarinic receptors may partly account for the effects of extrinsic denervation.
为了探究去神经超敏反应会增加外在去神经支配后回结肠运动活性这一假说，我们比较了分离的、具有外在神经支配或外在去神经支配的犬回结肠肠袢中的毒蕈碱神经传递。我们记录了回肠、回结肠括约肌（ICS）和结肠压力，以及回肠扩张期间的结肠张力、顺应性和舒张情况。通过新斯的明和最低有效剂量的毒蕈碱受体拮抗剂来探究毒蕈碱效应。去神经支配增强了回肠、ICS和结肠的收缩活性；结肠高幅传播收缩（HAPCs）也增强；回肠扩张期间的结肠舒张被消除。新斯的明在两种肠袢制剂中均诱导出HAPCs。哌仑西平（M1拮抗剂）降低了所有肠袢中的回肠收缩活性，并降低了有神经支配肠袢中回肠扩张期间的结肠舒张。哌仑西平还降低了结肠张力和结肠HAPCs，在去神经支配的肠袢中作用更明显。在所有肠袢中，达非那新（M3拮抗剂）比AF-DX 116（M2拮抗剂）更能降低回结肠收缩活性和张力。胆碱能受体亚型调节犬回结肠区域回结肠运动活性的不同方面。M1毒蕈碱受体敏感性增加可能部分解释了外在去神经支配的作用。
