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The Presence of Cal...
The Presence of Calcitonin Gene-Related Peptide and Its Receptors in Rat, Pig and Human Brain : Species Differences in Calcitonin Gene-Related Peptide Pharmacology
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- Warfvinge, Karin (författare)
- Lund University,Lunds universitet,Experimentell kärlforskning,Forskargrupper vid Lunds universitet,Experimental Vascular Research,Lund University Research Groups,Copenhagen University Hospital
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- Edvinsson, Lars (författare)
- Lund University,Lunds universitet,Experimentell kärlforskning,Forskargrupper vid Lunds universitet,Experimental Vascular Research,Lund University Research Groups,Copenhagen University Hospital
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- Pickering, Darryl S. (författare)
- University of Copenhagen
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- Sheykhzade, Majid (författare)
- University of Copenhagen
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(creator_code:org_t)
- 2019-09-04
- 2019
- Engelska.
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Ingår i: Pharmacology. - : S. Karger AG. - 0031-7012 .- 1423-0313. ; 104:5-6, s. 332-341
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Aim: The aim of present study is to investigate the binding characteristics of non-peptide calcitonin gene-related peptide (CGRP) receptor antagonists (i.e., gepants) in the brain membranes of rat, pig and human. Methods: The interaction of available gepants with the CGRP receptor was studied in the brain membranes of 3 different species using a radioligand competitive binding assay. In addition, the distribution of CGRP and its receptor component receptor activity modifying protein 1 (RAMP1) in rat cerebellum and cortex was explored using immunohistochemistry. Results: All gepants, except SB268262, displaced 100% of the radioligand specific binding in the brain tissue of all 3 species and showed highest affinity for CGRP receptors in human brain as compared to rat and pig brain membranes. Furthermore, radioligand binding studies revealed the presence of higher CGRP receptor density in human cerebellum compared to human cortex. The morphology, size and density of CGRP immunoreactive cells suggest that all cerebral cortical neurons were positive for CGRP. Slender receptor immunoreactive fibres were found spanning through the entire cortex. CGRP immunoreactivity was displayed in the cell soma of cerebellar Purkinje cells and in large neurons in the medial cerebellar nucleus. RAMP1 was found on the surface of the Purkinje cells and in parallel fibres, indicating presence in the granule cell axons. Conclusion: Cerebellum and cerebral cortex are rich in CGRP and CGRP receptors, which can be antagonized by gepants. However, all gepants display higher affinity for human CGRP receptors as compared to rat and pig CGRP receptors. Furthermore, human cerebellum seems to express higher density of CGRP receptors.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
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