Grider J R
Department of Physiology, Medical College of Virginia, Richmond 23298.
Am J Physiol. 1994 Jun;266(6 Pt 1):G1139-45. doi: 10.1152/ajpgi.1994.266.6.G1139.
The presence of calcitonin gene-related peptide (CGRP) in enteric and dorsal root ganglion neurons suggests that it might be involved as a transmitter in the sensory pathway that mediates the peristaltic reflex. This notion was examined in a three-compartment flat-sheet colonic preparation in which stimuli (muscle stretch or mucosal stimulation) were applied to the central compartment, while ascending contraction and descending relaxation were measured in the peripheral compartments. Both muscle stretch and mucosal stroking applied to the central compartment elicited CGRP release into the central, but not peripheral, compartments. The magnitude of release was proportional to the intensity of stimulation. Addition of the CGRP antagonists, human CGRP-(8-37) and [Tyr0]CGRP-(28-37), to the central compartment inhibited descending and ascending responses elicited by muscle stretch or mucosal stimulation. Addition of the sensory neurotoxin, capsaicin (0.01 to 1 microM), to the central compartment caused concentration-dependent release of CGRP; the resultant depletion of sensory transmitter resulted in a concentration-dependent decrease in ascending and descending responses elicited by muscle stretch and mucosal stimulation. Extrinsic denervation decreased basal CGRP release and abolished CGRP release and peristaltic responses normally elicited by muscle stretch but not CGRP release or peristaltic responses elicited by mucosal stimulation. The results indicate that extrinsic sensory pathways, which mediate the peristaltic response to muscle stretch, and intrinsic sensory pathways, which mediate the peristaltic response to mucosal stimulation, utilize CGRP as a sensory transmitter.
降钙素基因相关肽（CGRP）存在于肠神经元和背根神经节神经元中，这表明它可能作为一种递质参与介导蠕动反射的感觉通路。在一个三室平板结肠标本中对这一概念进行了研究，在该标本中，将刺激（肌肉拉伸或黏膜刺激）施加于中间隔室，同时在周边隔室测量向上的收缩和向下的舒张。施加于中间隔室的肌肉拉伸和黏膜抚摸均引起CGRP释放到中间隔室而非周边隔室。释放量与刺激强度成正比。向中间隔室添加CGRP拮抗剂人CGRP-（8-37）和[Tyr0]CGRP-（28-37）可抑制由肌肉拉伸或黏膜刺激引起的向下和向上反应。向中间隔室添加感觉神经毒素辣椒素（0.01至1微摩尔）导致CGRP浓度依赖性释放；感觉递质的最终耗竭导致由肌肉拉伸和黏膜刺激引起的向上和向下反应浓度依赖性降低。外在去神经支配降低了基础CGRP释放，并消除了通常由肌肉拉伸引起的CGRP释放和蠕动反应，但并未消除由黏膜刺激引起的CGRP释放或蠕动反应。结果表明，介导对肌肉拉伸的蠕动反应的外在感觉通路以及介导对黏膜刺激的蠕动反应的内在感觉通路利用CGRP作为感觉递质。
