Small fibronectin fragments induce endothelium-dependent vascular relaxations.
Strips of rabbit thoracic aorta precontracted with phenylephrine relaxed when exposed to selected synthetic peptides derived from the cell attachment domain of fibronectin. The relaxations elicited by both acetylcholine and the hexapeptide Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) were dependent on the presence of an intact endothelium, were resistant to indomethacin, and were inhibited by hemoglobin. The structure-activity relationship of four oligopeptides derived from fibronectin was in fair agreement with their ability to prevent fibronectin-mediated cell adhesion in other experimental systems. Human plasma fibronectin (up to 2.3 microM) did not relax this preparation and did not prevent the relaxant effect of the synthetic hexapeptide GRGDSP. On the rabbit isolated mesenteric artery, the relaxations induced by GRGDSP were significantly inhibited by indomethacin treatment, suggesting a contribution of locally produced prostaglandins. The displacement of fibronectin by soluble peptides from its binding sites on endothelial cells may result in significant pharmacologic responses, probably resulting from perturbations of the endothelial cell membranes.
Laplante
C
C
Unité de recherche inflammation et immunologie-rhumatologie, Centre hospitalier de l'Université Laval, Québec, Canada.
St-Pierre
S
S
Beaulieu
A D
AD
Marceau
F
F
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology*; D005353:Fibronectins / Q000494:pharmacology*; D006454:Hemoglobins / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D011817:Rabbits
D005353:Fibronectins; D006454:Hemoglobins; D010446:Peptide Fragments; D000109:Acetylcholine; D007213:Indomethacin