Departments of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, United States.
Alder Biopharmaceuticals Inc., Bothell, WA 98011, United States.
Neuropeptides. 2017 Aug;64:95-99. doi: 10.1016/j.npep.2016.11.004. Epub 2016 Nov 14.
The multifunctional neuropeptide calcitonin gene-related peptide (CGRP) and its receptor are expressed throughout the gastrointestinal tract. Previous studies have shown that CGRP has roles in intestinal motility, water secretion, and inflammation. Furthermore, animal studies have demonstrated CGRP involvement in diarrhea secondary to C. difficile and food allergies. Diarrhea thus provides a convenient bioassay of CGRP activity in the GI system. In this proof of principle study, we report that prophylactic administration of an anti-CGRP antibody is able to block CGRP-induced diarrhea in mice. As a control, the CGRP-receptor antagonist olcegepant also attenuated the diarrhea response to CGRP. This preclinical study indicates that anti-CGRP antibodies may provide a new preventative therapy for gastrointestinal disorders involving CGRP.
多功能神经肽降钙素基因相关肽（CGRP）及其受体在整个胃肠道中表达。先前的研究表明，CGRP 在肠道动力、水分泌和炎症中发挥作用。此外，动物研究表明 CGRP 参与了艰难梭菌和食物过敏引起的腹泻。因此，腹泻为胃肠道中 CGRP 活性提供了一种方便的生物测定方法。在这项原理验证研究中，我们报告称，预防性给予抗 CGRP 抗体能够阻止 CGRP 诱导的小鼠腹泻。作为对照，CGRP 受体拮抗剂 olcegepant 也减弱了 CGRP 引起的腹泻反应。这项临床前研究表明，抗 CGRP 抗体可能为涉及 CGRP 的胃肠道疾病提供一种新的预防治疗方法。
