Journal article
Calcitonin gene-related peptide receptor activation by receptor activity-modifying protein-1 gene transfer to vascular smooth muscle cells
Endocrinology (Philadelphia), Vol.147(4), pp.1932-1940
2006
DOI: 10.1210/en.2005-0918
PMID: 16373421
Abstract
The neuropeptide calcitonin gene-related peptide (CGRP) is a potent vasodilator that plays a protective role in the cardiovascular system. The receptor for CGRP is an unusual complex of the G protein-coupled calcitonin-like receptor and an obligate receptor activity modifying protein-1 (RAMP1). In this report we provide the first evidence that RAMP1 is rate limiting in vascular smooth muscle cells. Although cultured rat aorta smooth muscle cells express calcitonin like-receptor and RAMP1, we found that CGRP is not a potent activator of the receptor. After overexpression of RAMP1 by adenoviral gene transfer, there was a striking increase in CGRP-induced production of cAMP, with a 75-fold decrease in the EC(50) and a 1.5-fold increase in the maximal response. The biological consequence of this increased receptor activity was observed in three different paradigms. First, RAMP1 gene transfer caused a CGRP-dependent decrease in cell proliferation. Second, RAMP1 and CGRP treatment led to a 3-fold greater free radical-induced reduction in cell number. Finally, RAMP1 gene transfer resulted in a 5-fold CGRP-dependent increase in terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling-positive apoptotic cells upon serum withdrawal. The mechanisms underlying these effects involved cAMP-dependent pathways. We propose that RAMP1 gene transfer may be an effective strategy for increasing the effectiveness of CGRP-induced decrease in restenosis after aortic angioplasty.
Details
- Title: Subtitle
- Calcitonin gene-related peptide receptor activation by receptor activity-modifying protein-1 gene transfer to vascular smooth muscle cells
- Creators
- Zhongming Zhang - Deportment of Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242, United StatesIan M DICKERSON - Department of Neurobiology and Anatomy, University of Rochester, Rochester, New York 14642, United StatesAndrew F RUSSO - Deportment of Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242, United States
- Resource Type
- Journal article
- Publication Details
- Endocrinology (Philadelphia), Vol.147(4), pp.1932-1940
- DOI
- 10.1210/en.2005-0918
- PMID
- 16373421
- NLM abbreviation
- Endocrinology
- ISSN
- 0013-7227
- eISSN
- 1945-7170
- Publisher
- Endocrine Society; Bethesda, MD
- Language
- English
- Date published
- 2006
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center
- Record Identifier
- 9984020750202771
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