Impairment of osteoblast growth by nitric oxide synthase inhibitors: an effect independent of nitric oxide and arginine transport inhibition.
The effect of various inhibitors of nitric oxide synthase (NOS) on three cell lines with osteoblastic phenotype was studied. N-Mono-methyl arginine (NMMA) inhibited the growth of MG63 and ROS 17/2.8 cells, and N-iminoethyl-ornithine (NIO) inhibited the growth of ROS 17/2.8. However, N-nitro-arginine (NA) and N-nitro-arginine-methyl ester (NAME) had no effect. None of the NOS inhibitors affected MC3T3 growth, in spite of blocking NO synthesis. NMMA and NIO also caused a marked decrease of arginine uptake by the three cell lines studied. These results indicate that some NOS inhibitors have antiproliferative effects which do not seem to be related to the inhibition of NOS activity or arginine uptake.
Riancho
J A
JA
Department of Internal Medicine, Hospital U.M. Valdecilla, University of Cantabria, Santander, Spain.
Zarrabeitia
M T
MT
Salas
E
E
González-Macías
J
J
D000818:Animals; D001120:Arginine / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D001120:Arginine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester