EDRF release from canine coronary artery by lectins.
1. The effect of wheat germ agglutinin (WGA), concanavalin A (Con A) and lentil lectin agglutinin (LCA) were investigated on pre-contracted canine coronary artery rings in vitro. 2. In endothelium-intact canine coronary artery, contracted with the thromboxane A2-analogue, U46619, WGA relaxed the tissue in a concentration-dependent manner, with an inhibitory concentration (IC50) of 112 +/- 17 nM (n = 6). In the absence of an endothelium, WGA did not cause any relaxation of the tissue. 3. In endothelium-intact canine coronary artery, contracted with the thromboxane A2-analogue, U46619. LCA relaxed the tissue in a concentration-dependent manner, with an inhibitory concentration (IC50) of 423.1 +/- 41 nM (n = 6). In the absence of an endothelium, LCA produced a 20.1 +/- 1.1% (n = 6) relaxation at the highest concentration tested (3 microM). 4. Concanavalin A (Con A) relaxed canine coronary artery in a partial endothelium-dependent manner with an IC50 of 104 +/- 19 nM on endothelium-intact coronary artery and an IC50 of 1.3 +/- 0.3 microM (n = 6) on endothelium-denuded tissues. 5. The relaxation effects of WGA were attenuated by 1 mM NG-monomethyl L-arginine (L-NMMA) and completely inhibited by haemoglobin (3 microM), methylene blue (10 microM) and LY 83583 (30 microM). Ibuprofen had no effect on WGA-induced relaxation. 6. The relaxant effects of WGA were reversed by addition of 20 mM N-acetyl-D-glucosamine (GlcNAc) and N-acetyl-D-galactosamine (Ga1NAc) but not by alpha-mannose, D-(+)-galactose, and beta-lactose, whereas the endothelin-dependent relaxations to LCA and Con A were unaffected. 7.The endothelium-dependent relaxation induced by the lectins was unaffected by pretreatment of the tissue with 1 microM atropine.8. In the absence of extracellular calcium, WGA was also able to release EDRF suggesting that WGA acts through a second messenger system to release intracellular calcium.9. We suggest that WGA acts as an agonist to release EDRF from endothelial cells possibly by binding to a sugar moiety, specific receptor or adhesion molecules on the endothelial cell surface.
Kleha
J F
JF
Cardiovascular Research, Berlex Biosciences, Richmond, California 94804.
Devesly
P
P
Johns
A
A
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D037102:Lectins / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D014909:Wheat Germ Agglutinins / Q000494:pharmacology; D019323:omega-N-Methylarginine
D037102:Lectins; D014909:Wheat Germ Agglutinins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001285:Atropine; D001120:Arginine