Induction of NG-monomethyl-L-arginine uptake: a mechanism for differential inhibition of NO synthases?

Am J Physiol. 1995 Sep;269(3 Pt 1):C750-6. doi: 10.1152/ajpcell.1995.269.3.C750.

Abstract

The properties, selectivity, and regulation of NG-monomethyl-L-arginine (L-NMMA) uptake were examined in a human cultured vascular endothelial cell line SGHEC-7 and murine macrophage J774 cells. In both cell types the uptake of L-[14C]NMMA was time and temperature dependent. In endothelial cells L-[14C]NMMA uptake occurred via a single saturable carrier-mediated system with an apparent Kt of 77 +/- 2 microM. In murine macrophage cells a saturable component with an apparent Kt of 51 +/- 6 microM and a nonsaturable component of L-NMMA uptake were identified. In both cell types uptake of L-[14C]NMMA (10 microM) was significantly inhibited in the presence of 100-fold excess of L-NMMA, asymmetric NG,NG-dimethyl-L-arginine (ADMA), symmetric NG,NG-dimethyl-L-arginine (SDMA), L-canavanine, L-arginine, and to a lesser extent D-arginine. Uptake of L-[14C]NMMA was inhibited weakly (approximately 30%) by NG-nitro-L-arginine, NG-nitro-L-arginine methyl ester, aminoguanidine, and L-citrulline. Incubation of macrophage J774 cells with lipopolysaccharide (LPS; 1 or 10 micrograms/ml) resulted in the induction of nitric oxide (NO) synthase activity determined by the accumulation of nitrite in the culture medium. In these cells an enhanced uptake of L-NMMA uptake was observed which was prevented by pretreatment with cycloheximide (1 microM) but not dexamethasone (1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / metabolism
  • Arginine / pharmacokinetics
  • Biological Transport
  • Cell Line
  • Citrulline / metabolism
  • Cytokines / pharmacology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism
  • Endotoxins / pharmacology
  • Humans
  • Kinetics
  • Macrophages / metabolism
  • Mice
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Time Factors
  • omega-N-Methylarginine

Substances

  • Cytokines
  • Endotoxins
  • omega-N-Methylarginine
  • Citrulline
  • Arginine
  • Nitric Oxide Synthase