Calcitonin gene-related peptide receptor in cultured vascular smooth muscle and endothelial cells

1988 ◽  
Vol 151 (3) ◽  
pp. 1113-1121 ◽  
Author(s):  
Yukio Hirata ◽  
Yasuyuki Takagi ◽  
Shoichiro Takata ◽  
Yuka Fukuda ◽  
Hiroki Yoshimi ◽  
...  
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.


1992 ◽  
Vol 70 (12) ◽  
pp. 1571-1575 ◽  
Author(s):  
L. W. Kline ◽  
P. K. T. Pang

Calcitonin gene related peptide has been shown to relax vascular and intestinal smooth muscle. This study examines the effects of calcitonin gene related peptide on cholecystokinin-induced contraction of guinea pig gallbladder strips in vitro. Calcitonin gene related peptide was found to cause a dose-dependent relaxation of cholecystokinin-induced tension, which was blocked by the calcitonin gene related peptide receptor antagonist human calcitonin gene related peptide8–37. Previous studies demonstrated that calcitonin gene related peptide acted directly on guinea pig gallbladder smooth muscle to inhibit acetylcholine- or KCl-induced contraction. The present results further confirm that calcitonin gene related peptide acts directly on the smooth muscle. In addition, the use of L-NG-nitroarginine methyl ester, glibenclamide, and other agents strongly suggests that calcitonin gene related peptide also acts by way of the nonadrenergic noncholinergic nervous system, to induce the relaxation of cholecystokinin-induced contraction observed in the guinea pig gallbladder strips.Key words: calcitonin gene related peptide, gallbladder, cholecystokinin.


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