Identification of inhibitors of nitric oxide synthase that do not interact with the endothelial cell L-arginine transporter.
The effects of inhibitors of nitric oxide (NO) synthase and other cationic amino acids on unidirectional L-arginine transport were studied in porcine aortic endothelial cells cultured in microwell plates or perfused in microcarrier columns. L-Homoarginine, L-lysine and L-ornithine inhibited transport of L-arginine. The NO synthase inhibitors NG-monomethyl-L-arginine and NG-iminoethyl-L-ornithine also reduced L-arginine uptake, whereas NG-nitro-L-arginine and its methyl-ester had no inhibitory effect. The ability to modulate selectively endothelial cell L-arginine transport or NO synthase activity will allow further characterization of the arginine transporter and its role in regulating NO biosynthesis.
Bogle
R G
RG
Vascular Biology Research Centre, King's College, London.
Moncada
S
S
Pearson
J D
JD
Mann
G E
GE
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D026905:Amino Acid Transport Systems; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D019323:omega-N-Methylarginine
D026905:Amino Acid Transport Systems; D002352:Carrier Proteins; D019335:Nitroarginine; D019323:omega-N-Methylarginine; C065027:N(G)-iminoethylornithine; D001120:Arginine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester