title: Anti-CGRP antibodies block CGRP-induced diarrhea in mice.
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.
authors.affiliation: Departments of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Kaiser
authors.affiliation: Departments of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Rea
authors.affiliation: Departments of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Adisa
authors.initials: A
authors.lastname: Kuburas
authors.affiliation: Alder Biopharmaceuticals Inc., Bothell, WA 98011, United States.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Kovacevich
authors.affiliation: Alder Biopharmaceuticals Inc., Bothell, WA 98011, United States.
authors.forename: Leon F
authors.initials: LF
authors.lastname: Garcia-Martinez
authors.affiliation: Department of Neurology, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Ana
authors.initials: A
authors.lastname: Recober
authors.affiliation: Departments of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, United States; Department of Neurology, University of Iowa, Iowa City, IA 52242, United States; Veterans Affairs Medical Center, Iowa City, IA 52246, United States. Electronic address: andrew-russo@uiowa.edu.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Russo
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology*; D003967:Diarrhea / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D008810:Mice, Inbred C57BL; D008881:Migraine Disorders / Q000276:immunology*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000276:immunology / Q000378:metabolism
chemical_list: D018015:Receptors, Calcitonin Gene-Related Peptide; D015740:Calcitonin Gene-Related Peptide
keywords: Anti-CGRP antibody; CGRP; Colitis; Diarrhea; Mouse model; Olcegepant