Neural barriers affect the action of nitric oxide synthase inhibitors in the intact chicken retina.
Nitric oxide synthase (NOS) activity, as measured by the formation of L-[3H]citrulline from L-[3H]arginine, was blocked by micromolar concentrations of NOS inhibitors in retinal homogenates, but concentrations approximately 20-3000 times higher were needed in intact retina. The higher concentrations could be related to transport of the NOS inhibitors into neuronal cells and/or their sequestration within glial cells. NG-monomethyl-L-arginine and N-iminoethyl-L-ornithine significantly inhibited L-[3H]arginine uptake, whereas N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine had little or no effect on L-[3H]arginine uptake. The high concentrations of the inhibitors needed to inhibit nitric oxide production in intact tissue and their different interactions with arginine uptake systems may explain some of the conflicting results on the activity of NOS inhibitors on a range of physiological parameters in vivo.
Wellard
J W
JW
Centre for Visual Sciences and Research School of Biological Sciences, Australian National University. wellard@rsbs-central.anu.edu.au
Miethke
P
P
Morgan
I G
IG
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001813:Blood-Retinal Barrier / Q000502:physiology*; D002645:Chickens / Q000502:physiology*; D002956:Citrulline / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D019331:NG-Nitroarginine Methyl Ester; D009474:Neurons / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000201:enzymology*; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D002956:Citrulline; C065027:N(G)-iminoethylornithine; D001120:Arginine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester