scholarly journals Colonic Vascular Conductance Increased by Daikenchuto via Calcitonin Gene-Related Peptide and Receptor-Activity Modifying Protein 1

2008 ◽  
Vol 150 (1) ◽  
pp. 78-84 ◽  
Author(s):  
Toru Kono ◽  
Takashi Koseki ◽  
Shinichi Chiba ◽  
Yoshiaki Ebisawa ◽  
Naoyuki Chisato ◽  
...  
Endocrinology ◽  
2006 ◽  
Vol 147 (4) ◽  
pp. 1932-1940 ◽  
Author(s):  
Zhongming Zhang ◽  
Ian M. Dickerson ◽  
Andrew F. Russo

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 EC50 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.


Sign in / Sign up

Export Citation Format

Share Document