Effects of calcitonin gene-related peptide (CGRP) on Ca2+-channel current of isolated smooth muscle cells from rat vas deferens

1992 ◽  
Vol 346 (5) ◽  
Author(s):  
Ken Nakazawa ◽  
Hiroshi Saito ◽  
Norio Matsuki
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vas Deferens ◽  
Muscle Cells ◽  
Calcitonin Gene Related Peptide ◽  
Rat Vas Deferens ◽  
Channel Current ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Isolated Smooth Muscle Cells

scholarly journals Calcitonin Gene-Related Peptide Receptor Activation by Receptor Activity-Modifying Protein-1 Gene Transfer to Vascular Smooth Muscle Cells

Endocrinology ◽  
2006 ◽  
Vol 147 (4) ◽  
pp. 1932-1940 ◽  
Author(s):  
Zhongming Zhang ◽  
Ian M. Dickerson ◽  
Andrew F. Russo
Keyword(s):  
Smooth Muscle ◽  
Gene Transfer ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Calcitonin Gene Related Peptide ◽  
Receptor Activity ◽  
Related Peptide ◽  
Calcitonin Gene

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