THE METABOLISM OF L-ARGININE AND ITS SIGNIFICANCE FOR THE BIOSYNTHESIS OF ENDOTHELIUM-DERIVED RELAXING FACTOR - L-GLUTAMINE INHIBITS THE GENERATION OF L-ARGININE BY CULTURED ENDOTHELIAL-CELLS

被引:141
作者
SESSA, WC [1 ]
HECKER, M [1 ]
MITCHELL, JA [1 ]
VANE, JR [1 ]
机构
[1] ST BARTHOLOMEWS HOSP,COLL MED,WILLIAM HARVEY RES INST,CHARTERHOUSE SQ,LONDON EC1M 6BQ,ENGLAND
关键词
D O I
10.1073/pnas.87.21.8607
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mechanism by which L-glutamine (L-Gln) inhibits the release of endothelium-derived relaxing factor from bovine aortic cultured endothelial cells was investigated. The intracellular concentration of L-arginine (L-Arg) in Arg-depleted endothelial cells was inversely related to the level of L-Gln. Removal of L-Gln from the culture medium (usually containing L-Gln at 2 mM) abolished the inhibitory effect of the culture medium on L-Arg generation. L-Gln (0.2 and 2 mM) but not D-Gln inhibited the generation of L-Arg by both Arg-depleted and nondepleted endothelial cells. L-Gln did not interfere with the uptake of L-Arg or the metabolism of L-Arg-L-Phe to L-Arg but inhibited the formation of L-Arg from L-citrulline (L-Cit), L-Cit-L-Phe, and N(G)-monomethyl-L-arginine. L-Gln also inhibited the conversion of L-[14C]Cit to L-[14C]Arg by Arg-depleted endothelial cells. However, L-Gln did no inhibit the conversion of L-argininosuccinic acid to L-Arg by endothelial cell homogenates. Thus, L-Gln interferes with the conversion of L-Cit to L-Arg probably by acting on argininosuccinate synthetase rather than argininosuccinate lyase. L-Gln also inhibited the generation of L-Arg by the monocyte-macrophage cell line J774 but had no effect on the conversion of L-Cit to L-Arg by these cells. As the release of endothelium-derived relaxing factor from cultured and non-cultured endothelial cells is limited by the availability of L-Arg, endogenous L-Gln may play a regulatory role in the biosynthesis of endothelium-derived relaxing factor.
引用
收藏
页码:8607 / 8611
页数:5
相关论文
共 28 条
[1]   INDUCIBLE CYTOSOLIC ENZYME-ACTIVITY FOR THE PRODUCTION OF NITROGEN-OXIDES FROM L-ARGININE IN HEPATOCYTES [J].
BILLIAR, TR ;
CURRAN, RD ;
STUEHR, DJ ;
STADLER, J ;
SIMMONS, RL ;
MURRAY, SA .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 168 (03) :1034-1040
[2]   ISOLATION OF NITRIC-OXIDE SYNTHETASE, A CALMODULIN-REQUIRING ENZYME [J].
BREDT, DS ;
SNYDER, SH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (02) :682-685
[3]  
DENUCCI G, 1988, P NATL ACAD SCI USA, V85, P2334
[4]   REGIONAL DISTRIBUTION OF EDRF NO-SYNTHESIZING ENZYME(S) IN RAT-BRAIN [J].
FORSTERMANN, U ;
GORSKY, LD ;
POLLOCK, JS ;
SCHMIDT, HHHW ;
HELLER, M ;
MURAD, F .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 168 (02) :727-732
[5]   DEPLETION OF ARTERIAL L-ARGININE CAUSES REVERSIBLE TOLERANCE TO ENDOTHELIUM-DEPENDENT RELAXATION [J].
GOLD, ME ;
BUSH, PA ;
IGNARRO, LJ .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 164 (02) :714-721
[6]   THE METABOLISM OF L-ARGININE AND ITS SIGNIFICANCE FOR THE BIOSYNTHESIS OF ENDOTHELIUM-DERIVED RELAXING FACTOR - CULTURED ENDOTHELIAL-CELLS RECYCLE L-CITRULLINE TO L-ARGININE [J].
HECKER, M ;
SESSA, WC ;
HARRIS, HJ ;
ANGGARD, EE ;
VANE, JR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (21) :8612-8616
[7]   ENDOTHELIAL-CELLS METABOLIZE NG-MONOMETHYL-L-ARGININE TO L-CITRULLINE AND SUBSEQUENTLY TO L-ARGININE [J].
HECKER, M ;
MITCHELL, JA ;
HARRIS, HJ ;
KATSURA, M ;
THIEMERMANN, C ;
VANE, JR .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 167 (03) :1037-1043
[8]   INHIBITION BY L-GLUTAMINE OF THE RELEASE OF ENDOTHELIUM-DERIVED RELAXING FACTOR FROM CULTURED ENDOTHELIAL-CELLS [J].
HECKER, M ;
MITCHELL, JA ;
SWIERKOSZ, TA ;
SESSA, WC ;
VANE, JR .
BRITISH JOURNAL OF PHARMACOLOGY, 1990, 101 (02) :237-239
[9]   MACROPHAGE CYTOTOXICITY - ROLE FOR L-ARGININE DEIMINASE AND IMINO-NITROGEN OXIDATION TO NITRITE [J].
HIBBS, JB ;
TAINTOR, RR ;
VAVRIN, Z .
SCIENCE, 1987, 235 (4787) :473-476
[10]   MACROPHAGE SYNTHESIS OF NITRITE, NITRATE, AND N-NITROSAMINES - PRECURSORS AND ROLE OF THE RESPIRATORY BURST [J].
IYENGAR, R ;
STUEHR, DJ ;
MARLETTA, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (18) :6369-6373