Sternini C, Anselmi L, Guerrini S, Cervio E, Pham T, Balestra B, Vicini R, Baiardi P, D'agostino G-L, Tonini M
CURE Digestive Diseases Research Center, Digestive Diseases Division, Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
Neuroscience. 2004;125(1):103-12. doi: 10.1016/j.neuroscience.2003.12.043.
Galanin effects are mediated by distinct receptors, galanin receptor 1 (GAL-R1), GAL-R2 and GAL-R3. Here, we analyzed 1) the role of GAL-R1 in cholinergic transmission and peristalsis in the guinea-pig ileum using longitudinal muscle-myenteric plexus preparations and intact segments of the ileum in organ bath, and 2) the distribution of GAL-R1 immunoreactivity in the myenteric plexus with immunohistochemistry and confocal microscopy. Galanin inhibited electrically stimulated contractions of longitudinal muscle-myenteric plexus preparations with a biphasic curve. Desensitization with 1 microM galanin suppressed the high potency phase of the curve, whereas the GAL-R1 antagonist, RWJ-57408 (1 microM), inhibited the low potency phase. Galanin (3 microM) reduced the longitudinal muscle contraction and the peak pressure, and decreased the compliance of the circular muscle. All these effects were antagonized by RWJ-57408 (1 or 10 microM). RWJ-57408 (10 microM) per se did not affect peristalsis parameters in normal conditions, nor when peristalsis efficiency was reduced by partial nicotinic transmission blockade with hexamethonium. In the myenteric plexus, GAL-R1 immunoreactivity was localized to neurons and to fibers projecting within the plexus and to the muscle. GAL-R1 was expressed mostly by cholinergic neurons and by some neurons containing vasoactive intestinal polypeptide or nitric oxide synthase. This study indicates that galanin inhibits cholinergic transmission to the longitudinal muscle via two separate receptors; GAL-R1 mediates the low potency phase. The reduced peristalsis efficiency could be explained by inhibition of the cholinergic drive, whereas the decreased compliance is probably due to inhibition of descending neurons and/or to the activation of an excitatory muscular receptor. Endogenous galanin does not appear to affect neuronal pathways subserving peristalsis in physiologic conditions via GAL-R1.
甘丙肽的作用是由不同的受体介导的,即甘丙肽受体1(GAL-R1)、GAL-R2和GAL-R3。在此,我们进行了如下分析:1)使用纵向肌-肌间神经丛标本以及置于器官浴槽中的完整回肠段,研究GAL-R1在豚鼠回肠胆碱能传递和蠕动中的作用;2)采用免疫组织化学和共聚焦显微镜技术,研究GAL-R1免疫反应性在肌间神经丛中的分布。甘丙肽以双相曲线抑制纵向肌-肌间神经丛标本的电刺激收缩。用1微摩尔甘丙肽进行脱敏处理可抑制曲线的高效能阶段,而GAL-R1拮抗剂RWJ-57408(1微摩尔)则抑制低效能阶段。甘丙肽(3微摩尔)可降低纵向肌收缩和峰值压力,并降低环行肌的顺应性。所有这些作用均被RWJ-57408(1或10微摩尔)拮抗。RWJ-57408(10微摩尔)本身在正常情况下不影响蠕动参数,在用六甲铵部分阻断烟碱传递从而降低蠕动效率时也不影响。在肌间神经丛中,GAL-R1免疫反应性定位于神经元、丛内投射的纤维以及肌肉。GAL-R1主要由胆碱能神经元以及一些含有血管活性肠肽或一氧化氮合酶的神经元表达。本研究表明,甘丙肽通过两种不同的受体抑制向纵向肌的胆碱能传递;GAL-R1介导低效能阶段。蠕动效率降低可能是由于胆碱能驱动受到抑制,而顺应性降低可能是由于下行神经元受到抑制和/或兴奋性肌肉受体被激活。内源性甘丙肽在生理条件下似乎不会通过GAL-R1影响维持蠕动的神经元通路。