Regional distribution and regulation of [125I]calcitonin gene-related peptide binding sites in coronary arteries.
Quantitative in vitro autoradiographic techniques were used to localize and characterize 125I-labelled human calcitonin gene-related peptide ([125I]hCGRP) binding sites in sections of bovine left anterior descending coronary artery (LAD). Specific high affinity (Kd 0.4 nM) [125I]hCGRP binding sites were localized to the media of both epicardial and myocardial coronary arteries. Binding site density was greater in distal epicardial and myocardial arteries than in proximal epicardial regions of the LAD. Binding sites exhibited a significantly higher affinity for alpha-hCGRP (Ki 1.1 nM) than for hCGRP-(8-37) (Ki 7.0 nM) and [Cys(ACM)2,7]hCGRP (Ki 27.4 nM). Guanosine-5'-O-(3-thiotriphosphate) inhibited [125I]hCGRP binding in a concentration-dependent manner. Extrinsic denervation of the bovine heart resulted in a depletion of CGRP-like immunoreactive perivascular nerve fibres and an increase in the density of coronary artery [125I]hCGRP binding sites (P = 0.0092). The regional distribution of binding sites in human coronary arteries differed from that observed in bovine and porcine vessels. It is concluded that selective, G protein-coupled, CGRP receptors are present in the media of bovine coronary arteries; there are both regional and species differences in the distribution of CGRP binding sites in coronary arteries and endogenous CGRP may exert a tonic influence on coronary vasomotor tone.
Knock
G A
GA
Department of Histochemistry, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Wharton
J
J
Gaer
J A
JA
Yacoub
M H
MH
Taylor
K M
KM
Polak
J M
JM
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002417:Cattle; D003331:Coronary Vessels / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D009479:Neuropeptides / Q000494:pharmacology; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000032:analysis*; D013552:Swine; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D009479:Neuropeptides; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D015740:Calcitonin Gene-Related Peptide