| Effect of two novel CGRP-binding compounds in a closed cranial window rat model. | |
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MedLine Citation:
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PMID: 17477918 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We investigated the in vivo effects of two novel calcitonin gene-related peptide (CGRP) binding molecules in the genuine closed cranial window model in the rat. The RNA-Spiegelmer (NOX-C89) and the monoclonal CGRP antibody are CGRP scavengers and might be used as an alternative to CGRP-receptor antagonists in the treatment of migraine. Rats were anaesthetized and a closed cranial window established. Changes in dural and pial artery diameter and mean arterial blood pressure were measured simultaneously. Infusion of the RNA-Spiegelmer or the CGRP antibody alone had no effect on the arteries or the mean arterial blood pressure. We then used a bolus of 0.3 microg/kg CGRP (n=6) or electrical stimulation (25 V, 5 Hz, 1 ms pulse width and of 10 s of duration) (n=6) to induce dilatation of dural and pial arteries (mediated via CGRP-receptors). Pre-treatment with the RNA-Spiegelmer inhibited CGRP-induced vasodilatation of the dural artery (from 38+/-17% to 7+/-3%) and the pial artery (from 14+/-1% to 3+/-2%) (P<0.05). The RNA-Spiegelmer, however, did not significantly inhibit dilatation induced by electrical stimulation (P>0.05). The CGRP antibody caused a significant reduction of the dural artery diameter caused by intravenous CGRP-infusion (from 23+/-5% to 12+/-3%) (P<0.05), but did not inhibit dilatation caused by electrical stimulation (P>0.05). In conclusion, the CGRP scavengers effectively inhibited the effect of circulating CGRP but do not modify the effect of electrical stimulation and the consequent liberation of CGRP from perivascular sensory nerve fibres. |
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Authors:
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Louise Juhl; Lars Edvinsson; Jes Olesen; Inger Jansen-Olesen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-04-14 |
Journal Detail:
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Title: European journal of pharmacology Volume: 567 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-05-28 Completed Date: 2007-07-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 117-24 Citation Subset: IM |
Affiliation:
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Department of Neurology, Glostrup Research Institute, Glostrup Hospital, University of Copenhagen, DK-2600, Glostrup, Denmark. loujuh01@glo.regionh.dk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / pharmacology* Aptamers, Nucleotide / pharmacology* Blood Pressure / drug effects Calcitonin Gene-Related Peptide / immunology, metabolism*, pharmacology Disease Models, Animal Dura Mater / blood supply Electric Stimulation Male Meningeal Arteries / drug effects, physiopathology Middle Cerebral Artery / drug effects, physiopathology Migraine Disorders / drug therapy Oligonucleotides / pharmacology* Pia Mater / blood supply Polyethylene Glycols / chemistry Protein Binding Rats Rats, Sprague-Dawley Vasodilation / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Aptamers, Nucleotide; 0/NOX-C29; 0/Oligonucleotides; 0/Polyethylene Glycols; 83652-28-2/Calcitonin Gene-Related Peptide |
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