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CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart. Circ Res 2002 May 03;90(8):844-9

Date

05/04/2002

Pubmed ID

11988484

DOI

10.1161/01.res.0000016164.02525.b4

Scopus ID

2-s2.0-0037013178 (requires institutional sign-in at Scopus site)   148 Citations

Abstract

Growth hormone-releasing peptides (GHRPs) are known as potent growth hormone secretagogues whose actions are mediated by the ghrelin receptor, a G protein-coupled receptor cloned from pituitary libraries. Hexarelin, a hexapeptide of the GHRP family, has reported cardiovascular activity. To identify the molecular target mediating this activity, rat cardiac membranes were labeled with a radioactive photoactivatable derivative of hexarelin and purified using lectin affinity chromatography and preparative gel electrophoresis. A binding protein of M(r) 84 000 was identified. The N-terminal sequence determination of the deglycosylated protein was identical to rat CD36, a multifunctional glycoprotein, which was expressed in cardiomyocytes and microvascular endothelial cells. Activation of CD36 in perfused hearts by hexarelin was shown to elicit an increase in coronary perfusion pressure in a dose-dependent manner. This effect was lacking in hearts from CD36-null mice and hearts from spontaneous hypertensive rats genetically deficient in CD36. The coronary vasoconstrictive response correlated with expression of CD36 as assessed by immunoblotting and covalent binding with hexarelin. These data suggest that CD36 may mediate the coronary vasospasm seen in hypercholesterolemia and atherosclerosis.

Author List

Bodart V, Febbraio M, Demers A, McNicoll N, Pohankova P, Perreault A, Sejlitz T, Escher E, Silverstein RL, Lamontagne D, Ong H

Author

Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Binding Sites
CD36 Antigens
Cell Membrane
Heart
Immunoblotting
Mice
Mice, Knockout
Myocardium
Oligopeptides
Organ Culture Techniques
Photoaffinity Labels
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Rats, Sprague-Dawley
Receptors, Neuropeptide
Receptors, Pituitary Hormone-Regulating Hormone
Vasoconstriction
Vasoconstrictor Agents