Calcitonin gene-related peptide in healthy and atheromatous human epicardial coronary arteries. Function and receptor characterization.
To examine the possible role of calcitonin gene-related peptide (CGRP) in the control of human coronary vascular tone, we have investigated the action of this peptide in healthy and atheromatous human epicardial coronary arteries and localised [125I]CGRP-binding sites in these vessels. Isolated arteries were obtained from 10 cardiomyopathic patients and 6 patients with ischaemic heart disease (IHD), who were undergoing heart transplantation. CGRP elicited concentration-dependent vasodilatation in preconstricted vessels. Both healthy and diseased coronary arteries exhibited similar maximum responses and sensitivity to this peptide. Removal of the endothelium did not diminish the vasodilator action of CGRP in non-atherosclerotic coronary arteries. [125I]CGRP bound to tissue sections in a concentration-dependent manner. Binding was similar in healthy and atheromatous vessels, with a Bmax value of 10.2 +/- 5.6 and 18.9 +/- 3.0 amol/mg protein, and dissociation constant (Kd) of 0.07 +/- 0.1 and 0.18 +/- 0.1 nM, respectively. Dense [125I]CGRP binding was mainly associated with vascular smooth muscle cells of both normal and diseased vessels with some patches of binding to regions of atherosclerotic plaque in vessels from patients with IHD. These data indicate that CGRP is a potent endothelium-independent vasodilator in the human coronary vasculature. The preservation of dilator function and CGRP receptor binding in atherosclerotic coronary arteries suggests that this peptide may play a role in the control or maintenance of vascular tone in certain disease states.
Luu
T N
TN
Department of Surgery, Harefield Hospital, UK.
Dashwood
M R
MR
Chester
A H
AH
Muddle
J R
JR
Yacoub
M H
MH
D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000503:physiopathology*; D001345:Autoradiography; D001665:Binding Sites; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D011869:Radioligand Assay; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000032:analysis*; D014655:Vascular Resistance / Q000187:drug effects
D018015:Receptors, Calcitonin Gene-Related Peptide; D015740:Calcitonin Gene-Related Peptide