Journal article
Anti-CGRP antibodies block CGRP-induced diarrhea in mice
Neuropeptides (Edinburgh), Vol.64, pp.95-99
08/2017
DOI: 10.1016/j.npep.2016.11.004
PMCID: PMC5429995
PMID: 27865545
Abstract
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.
•CGRP antibodies may provide a novel therapeutic tool in the management of diarrhea and other GI pathologies.•CGRP antibodies actions in the GI system may also complement their use for prophylactic treatment of migraine.
Details
- Title: Subtitle
- Anti-CGRP antibodies block CGRP-induced diarrhea in mice
- Creators
- Eric A Kaiser - Departments of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, United StatesBrandon J Rea - Departments of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, United StatesAdisa Kuburas - Departments of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, United StatesBrian R Kovacevich - Alder Biopharmaceuticals Inc., Bothell, WA 98011, United StatesLeon F Garcia-Martinez - Alder Biopharmaceuticals Inc., Bothell, WA 98011, United StatesAna Recober - Department of Neurology, University of Iowa, Iowa City, IA 52242, United StatesAndrew F Russo - Departments of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Neuropeptides (Edinburgh), Vol.64, pp.95-99
- DOI
- 10.1016/j.npep.2016.11.004
- PMID
- 27865545
- PMCID
- PMC5429995
- NLM abbreviation
- Neuropeptides
- ISSN
- 0143-4179
- eISSN
- 1532-2785
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: NS075599, F30 NS067887; name: Alder Biopharmaceuticals
- Language
- English
- Date published
- 08/2017
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Neurology (Pediatrics)
- Record Identifier
- 9984020900202771
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