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EDRF release from canine coronary artery by lectins
J F Kleha1, P Devesly, A Johns
1Cardiovascular Research, Berlex Biosciences, Richmond, California 94804.
British Journal of Pharmacology
|December 1, 1993
Summary
Wheat germ agglutinin (WGA) and other lectins cause endothelium-dependent relaxation in canine coronary arteries. WGA releases endothelial-derived relaxing factor (EDRF) by interacting with endothelial cell surface molecules.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Biochemistry
Background:
- Lectins are proteins that bind carbohydrates and can interact with cell surface molecules.
- Endothelial-derived relaxing factor (EDRF) plays a crucial role in regulating vascular tone.
- Canine coronary arteries are a common model for studying vascular function.
Purpose of the Study:
- To investigate the effects of wheat germ agglutinin (WGA), concanavalin A (Con A), and lentil lectin agglutinin (LCA) on canine coronary artery rings in vitro.
- To elucidate the mechanisms underlying lectin-induced relaxation, particularly the role of the endothelium and EDRF.
Main Methods:
- Canine coronary artery rings were pre-contracted with U46619, a thromboxane A2 analogue.
- Relaxation responses to WGA, Con A, and LCA were measured in endothelium-intact and endothelium-denuded tissues.
- The involvement of EDRF was assessed using inhibitors like NG-monomethyl L-arginine (L-NMMA), hemoglobin, methylene blue, and LY 83583.
- The role of specific sugar moieties in lectin binding was investigated using competitive inhibition with various sugars.
Main Results:
- WGA induced concentration-dependent relaxation in endothelium-intact coronary arteries, an effect absent in denuded tissues.
- LCA and Con A also exhibited relaxation, with Con A showing partial endothelium-dependence.
- WGA-induced relaxation was attenuated by L-NMMA and inhibited by EDRF pathway blockers, suggesting EDRF involvement.
- WGA-induced relaxation was reversed by N-acetyl-D-glucosamine and N-acetyl-D-galactosamine, indicating binding to specific sugar residues.
- WGA released EDRF even in the absence of extracellular calcium, suggesting intracellular signaling pathways.
Conclusions:
- WGA acts as an agonist to release EDRF from endothelial cells, likely through binding to specific sugar moieties or adhesion molecules.
- The endothelium plays a critical role in the relaxant effects of WGA, Con A, and LCA on canine coronary arteries.
- WGA may activate intracellular signaling pathways to promote EDRF release.