Agmatine activation of nitric oxide synthase in endothelial cells.
Agmatine is a product of arginine decarboxylation. Systemic infusion of agmatine into rats causes hypotension. This effect could be due either to a central action of agmatine (a clonidine displacing substance), or to a direct effect of agmatine on cells of blood vessel walls, which induces them to cause vasodilatation, or both. In this study, we examined the effects of agmatine on endothelial cell function by using cultured bovine pulmonary artery endothelial cells. Agmatine stimulated nitrite production three-fold above basal nitrite formation by endothelial cells. The increased nitrite production by agmatine was inhibited by idazoxan but not by yohimbine. Agmatine displaced [3H]-idazoxan from endothelial cell membranes and was found to induce transients in the cytosolic calcium of endothelial cells. The transients could be downregulated by repeated exposure to agmatine but were not affected by pretreatment with norepinephrine. These results suggest that agmatine can bind to a cell surface imidazoline receptor on endothelial cells and can stimulate nitric oxide production by increasing cytosolic calcium. Therefore, agmatine appears to act directly on endothelial cells to increase the synthesis of nitric oxide, a vasodilatory substance.
Morrissey
J J
JJ
Department of Internal Medicine, Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, MO 63110, USA.
Klahr
S
S
D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism
D009573:Nitrites; D000376:Agmatine; D019001:Nitric Oxide Synthase; D002118:Calcium