Grider John R
Department of Physiology, P.O. Box 980551, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA.
J Pharmacol Exp Ther. 2003 Nov;307(2):460-7. doi: 10.1124/jpet.103.053512. Epub 2003 Sep 9.
The motor, modulatory, and sensory neurotransmitters that mediate the peristaltic reflex in the mouse colon were identified by direct measurement, and their involvement in various pathways was determined by selective receptor antagonists. Mucosal stimulation in the central compartment of a three-compartment flat sheet preparation of mouse colon elicited ascending contraction and descending relaxation in the orad and caudad compartments, respectively. Ascending contraction was accompanied by substance P release, a marker for excitatory neurotransmitter release, into the orad compartment and was partly inhibited by atropine and spantide, and abolished by a combination of the two antagonists. Descending relaxation was accompanied by vasoactive intestinal peptide (VIP) release, a marker for inhibitory neurotransmitter release, into the caudad compartment, and was partly inhibited by VIP10-28 and NG-nitro-L-arginine, and abolished by a combination of the two agents. Somatostatin release increased during descending relaxation: immunoneutralization of somatostatin or blockade of its effect with a selective somatostatin type 2 receptor antagonist inhibited descending relaxation. The delta-opioid receptor antagonist naltrindole augmented descending relaxation and ascending contraction. Calcitonin gene-related peptide (CGRP) release increased in the central compartment and was mediated by concurrent release of 5-hydroxytryptamine (5-HT) because its release was blocked by a 5-HT4 receptor antagonist. Both the latter and the CGRP antagonist CGRP8-37, inhibited ascending contraction and descending relaxation. Thus, the reflex in mouse like that in rat and human intestine is initiated by mucosal release of 5-HT and activation of 5-HT4 receptors on CGRP sensory neurons and is relayed via somatostatin and opioid interneurons to VIP/nitric-oxide synthase inhibitory motor neurons and via cholinergic interneurons to acetylcholine/tachykinin excitatory motor neurons.
通过直接测量确定了介导小鼠结肠蠕动反射的运动、调节和感觉神经递质，并通过选择性受体拮抗剂确定了它们在各种途径中的作用。在小鼠结肠三室平板制剂的中央隔室进行黏膜刺激，分别在口腔和尾侧隔室引起上行收缩和下行松弛。上行收缩伴随着P物质释放（兴奋性神经递质释放的标志物）进入口腔隔室，部分被阿托品和spantide抑制，两种拮抗剂联合使用则可消除该效应。下行松弛伴随着血管活性肠肽（VIP）释放（抑制性神经递质释放的标志物）进入尾侧隔室，部分被VIP10-28和NG-硝基-L-精氨酸抑制，两种药物联合使用则可消除该效应。下行松弛期间生长抑素释放增加：生长抑素的免疫中和或用选择性2型生长抑素受体拮抗剂阻断其作用可抑制下行松弛。δ-阿片受体拮抗剂纳曲吲哚增强了下行松弛和上行收缩。降钙素基因相关肽（CGRP）在中央隔室释放增加，由5-羟色胺（5-HT）的同时释放介导，因为其释放被5-HT4受体拮抗剂阻断。后者和CGRP拮抗剂CGRP8-37均抑制上行收缩和下行松弛。因此，小鼠的这种反射与大鼠和人类肠道的反射一样，由5-HT的黏膜释放和CGRP感觉神经元上5-HT4受体的激活引发，并通过生长抑素和阿片中间神经元传递至VIP/一氧化氮合酶抑制性运动神经元，以及通过胆碱能中间神经元传递至乙酰胆碱/速激肽兴奋性运动神经元。
