دورية أكاديمية
Characterization of erenumab and rimegepant on calcitonin gene-related peptide induced responses in Xenopus Laevis oocytes expressing the calcitonin gene-related peptide receptor and the amylin-1 receptor
| العنوان: | Characterization of erenumab and rimegepant on calcitonin gene-related peptide induced responses in Xenopus Laevis oocytes expressing the calcitonin gene-related peptide receptor and the amylin-1 receptor |
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| المؤلفون: | Sanne Hage La Cour, Kiki Juhler, Lisette J. A. Kogelman, Jes Olesen, Dan Arne Klærke, David Møbjerg Kristensen, Inger Jansen-Olesen |
| المصدر: | The Journal of Headache and Pain, Vol 23, Iss 1, Pp 1-12 (2022) |
| بيانات النشر: | BMC, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine |
| مصطلحات موضوعية: | Migraine, CGRP, Xenopus Laevis oocytes, Amylin, Amylin receptor, RAMP1, Medicine |
| الوصف: | Abstract Background The clinical use of calcitonin gene-related peptide receptor (CGRP-R) antagonists and monoclonal antibodies against CGRP and CGRP-R has offered new treatment possibilities for migraine patients. CGRP activates both the CGRP-R and structurally related amylin 1 receptor (AMY1-R). The relative effect of erenumab and the small-molecule CGRP-R antagonist, rimegepant, towards the CGRP-R and AMY-R needs to be further characterized. Methods The effect of CGRP and two CGRP-R antagonists were examined in Xenopus laevis oocytes expressing human CGRP-R, human AMY1-R and their subunits. Results CGRP administered to receptor expressing oocytes induced a concentration-dependent increase in current with the order of potency CGRP-R> > AMY1-R > calcitonin receptor (CTR). There was no effect on single components of the CGRP-R; calcitonin receptor-like receptor and receptor activity-modifying protein 1. Amylin was only effective on AMY1-R and CTR. Inhibition potencies (pIC50 values) for erenumab on CGRP induced currents were 10.86 and 9.35 for CGRP-R and AMY1-R, respectively. Rimegepant inhibited CGRP induced currents with pIC50 values of 11.30 and 9.91 for CGRP-R and AMY1-R, respectively. Conclusion Our results demonstrate that erenumab and rimegepant are potent antagonists of CGRP-R and AMY1-R with 32- and 25-times preference for the CGRP-R over the AMY1-R, respectively. It is discussed if this difference in affinity between the two receptors is the likely reason why constipation is a common and serious adverse effect during CGRP-R antagonism but less so with CGRP binding antibodies. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1129-2369 1129-2377 |
| العلاقة: | https://doaj.org/toc/1129-2369Test; https://doaj.org/toc/1129-2377Test |
| DOI: | 10.1186/s10194-022-01425-9 |
| الوصول الحر: | https://doaj.org/article/4da325ce717d444799c82d731c83299aTest |
| رقم الانضمام: | edsdoj.4da325ce717d444799c82d731c83299a |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 11292369 11292377 |
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| DOI: | 10.1186/s10194-022-01425-9 |