CGRP receptor activity in mice with global expression of human receptor activity modifying protein 1 Article Swipe
Keegan J Bohn
,
Baolin Li
,
Xiaofang Huang
,
Bianca N. Mason
,
Anne‐Sophie Wattiez
,
Adisa Kuburas
,
Christopher S. Walker
,
Peiyi Yang
,
Jianliang Yu
,
Beverly A. Heinz
,
Kirk W. Johnson
,
Andrew F. Russo
·
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1111/bph.13783
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1111/bph.13783
Background and Purpose CGRP is a potent vasodilator and nociceptive neuropeptide linked to migraine. CGRP receptors are heterodimers of receptor activity modifying protein 1 (RAMP1) and either calcitonin receptor‐like receptor (CLR; forms canonical CGRP receptor) or calcitonin receptor (CT receptor; forms AMY 1 receptor). The goal of this study was to test whether transgenic mice globally expressing human RAMP1 have increased CGRP receptor activity and whether the receptors are sensitive to human selective antagonist telcagepant. Experimental Approach cAMP production was measured in primary cultures of aortic smooth muscle and trigeminal ganglia neurons from global hRAMP1 mice and non‐transgenic littermates. Functional activity and inhibition were compared with clonal cell lines expressing combinations of CLR or CT receptors with RAMP1. Key Results Cultured smooth muscle from global hRAMP1 mice had a 10‐fold greater CGRP‐induced cAMP maximal response (Rmax) than non‐transgenic littermates, with similar EC 50 s. In contrast, cultured trigeminal ganglia from global hRAMP1 mice had a 40‐fold leftward shift of the EC 50 , with similar Rmax values as littermates. In both hRAMP1 cultures, telcagepant blocked CGRP‐induced cAMP production, but was not effective in non‐transgenic cultures. IC 50 values were closer to those observed for CT receptor/hRAMP1 than CLR/hRAMP1 in clonal cell lines. Conclusions and Implications Overexpression of hRAMP1 increases CGRP signalling by changing the maximal response or ligand sensitivity, depending on tissue type. Furthermore, telcagepant inhibited transgenic hRAMP1 CGRP receptors, but the degree of inhibition suggests that the transgenic mice are only partially humanized or both canonical CGRP and AMY 1 receptors are functional in trigeminal ganglia neurons and vascular smooth muscle.
Related Topics
Concepts
Calcitonin gene-related peptide
Receptor
Internal medicine
Endocrinology
Calcitonin receptor
Receptor antagonist
Trigeminal ganglion
Biology
Chemistry
Cell biology
Antagonist
Neuropeptide
Neuroscience
Medicine
Sensory system
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1111/bph.13783
- https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bph.13783
- OA Status
- bronze
- Cited By
- 19
- References
- 50
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2603213603
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2603213603Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1111/bph.13783Digital Object Identifier
- Title
-
CGRP receptor activity in mice with global expression of human receptor activity modifying protein 1Work title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2017Year of publication
- Publication date
-
2017-03-20Full publication date if available
- Authors
-
Keegan J Bohn, Baolin Li, Xiaofang Huang, Bianca N. Mason, Anne‐Sophie Wattiez, Adisa Kuburas, Christopher S. Walker, Peiyi Yang, Jianliang Yu, Beverly A. Heinz, Kirk W. Johnson, Andrew F. RussoList of authors in order
- Landing page
-
https://doi.org/10.1111/bph.13783Publisher landing page
- PDF URL
-
https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bph.13783Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
-
https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bph.13783Direct OA link when available
- Concepts
-
Calcitonin gene-related peptide, Receptor, Internal medicine, Endocrinology, Calcitonin receptor, Receptor antagonist, Trigeminal ganglion, Biology, Chemistry, Cell biology, Antagonist, Neuropeptide, Neuroscience, Medicine, Sensory systemTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
19Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 1, 2022: 6, 2021: 3, 2020: 2, 2019: 2Per-year citation counts (last 5 years)
- References (count)
-
50Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| primary_location.raw_type | journal-article |
| primary_location.license_id | |
| primary_location.is_accepted | True |
| primary_location.is_published | True |
| primary_location.raw_source_name | British Journal of Pharmacology |
| primary_location.landing_page_url | https://doi.org/10.1111/bph.13783 |
| publication_date | 2017-03-20 |
| publication_year | 2017 |
| referenced_works | https://openalex.org/W2196303538, https://openalex.org/W2025496772, https://openalex.org/W2124879125, https://openalex.org/W2332204995, https://openalex.org/W2165757744, https://openalex.org/W1596457615, https://openalex.org/W2040177399, https://openalex.org/W1999180573, https://openalex.org/W1558116296, https://openalex.org/W1970846628, https://openalex.org/W2086714349, https://openalex.org/W2098082628, https://openalex.org/W2052258972, https://openalex.org/W2134152362, https://openalex.org/W2163718694, https://openalex.org/W2083214820, https://openalex.org/W2038399206, https://openalex.org/W2137924809, https://openalex.org/W1973662774, https://openalex.org/W2135858080, https://openalex.org/W2098988727, https://openalex.org/W2166749253, https://openalex.org/W2091778618, https://openalex.org/W1593555249, https://openalex.org/W2286424816, https://openalex.org/W2058172887, https://openalex.org/W2162942726, https://openalex.org/W2077658538, https://openalex.org/W2047455969, https://openalex.org/W2150391797, https://openalex.org/W1888470382, https://openalex.org/W2085447391, https://openalex.org/W2048132386, https://openalex.org/W1603155066, https://openalex.org/W2129889492, https://openalex.org/W1966481705, https://openalex.org/W2122818778, https://openalex.org/W2161310038, https://openalex.org/W2194756172, https://openalex.org/W2162104155, https://openalex.org/W2084937412, https://openalex.org/W2119565450, https://openalex.org/W2011893236, https://openalex.org/W2074939801, https://openalex.org/W1895103031, https://openalex.org/W2587308265, https://openalex.org/W1533486949, https://openalex.org/W1999856566, https://openalex.org/W2038864055, https://openalex.org/W2001306967 |
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