Characterization of L-arginine transport by pulmonary artery endothelial cells

Greene, Bruce D.; Pacitti, Anthony J.; Souba, Wiley W.

doi:10.1152/ajplung.1993.264.4.l351

Cited by 36 publications

(42 citation statements)

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“…2). These data are consistent with Na¤-dependent ¬_arginine transport mediated by a B°, + -like system, which was identified by Van Winkle et al (1985) in blastocytes, and later described in pulmonary artery endothelial cells (Greene et al 1993;McDonald et al 1997) and small intestine (Munck & Munck, 1995). Apparently, the Na¤-independent y¤-like system corresponds to the lower Km component described in Fig.…”

Section: Effect Of Aspirin On Placental Uptake Of ¬_[åh]argininesupporting

confidence: 91%

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L-Arginine Transport at the Fetal Side of Human Placenta: Effect of Aspirin in Pregnancy

ACEVEDO¹,

ROJAS²,

BRAVO³

1999

Exp. Physiol.

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summary ¬_Arginine transport by the fetal side of human placenta was investigated through the characterization of ¬_ [ÅH]arginine uptake in isolated perfused cotyledon. Competitive inhibition experiments suggest the presence of at least two transport systems: a Na¤-independent, pHinsensitive system inhibitable by cationic amino acids, similar to system y¤, and a Na¤-dependent system which recognizes both cationic and neutral amino acids only in the presence of Na¤, i.e. a B°, + -like system. The kinetic analysis of ¬-arginine uptake in the presence of Na¤ revealed that the process is mediated by saturable components: a high-affinity system (Km = 167 ± 18·0 ìÒ; Vmax = 0·174 ± 0·012 ìmol min¢) and a low-affinity carrier (Km = 980 ± 112 ìÒ; Vmax = 1·60 ± 0·12 ìmol min¢). In the absence of Na¤, ¬_arginine uptake was fitted by one model with a Michaelis-Menten constant of 200 ± 24·8 ìÒ. These results suggest that the high-affinity component corresponds to the Na¤-independent system y¤, whilst the low-affinity system may represent the activity of the Na¤-dependent B°, + transporter. Kinetic studies in placentae taken from aspirin-treated pregnancies showed that ¬_arginine is transported with a significantly higher affinity (Km = 42·5 ± 5·7 ìÒ), but with a lower capacity (Vmax = 0·064 ± 0·003 ìmol min¢) than in the non-treated group. The latter finding suggests that aspirin would facilitate the uptake of the NO precursor only at very low arginine concentrations.

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Section: Effect Of Aspirin On Placental Uptake Of ¬_[åh]argininesupporting

confidence: 91%

“…1) might correspond to the Na¤-dependent B°, + transport system. However, the Km value determined in our study is higher than those currently described for the B°, + transporter in other cell types (Greene et al 1993;Van Winkle et al 1985).…”

Section: Effect Of Aspirin On Placental Uptake Of ¬_[åh]argininecontrasting

confidence: 74%

L-Arginine Transport at the Fetal Side of Human Placenta: Effect of Aspirin in Pregnancy

ACEVEDO¹,

ROJAS²,

BRAVO³

1999

Exp. Physiol.

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“…Experiments were also performed following removal of the endothelium. The requirement for L-arginine uptake was examined by addition of 10 mM L-lysine as a competitive inhibitor of both Na + independent (system y + ) and Na + dependent transport (Greene et al, 1993); 10 mM mannitol was used as an osmotic control. Experiments were time matched in separate arteries.…”

Section: Experimental Protocolsmentioning

confidence: 99%

“…Either value is close to the EC 50 for L-arginine that we have previously reported for potentiation of tetramethylpyrazine-induced relaxation (*1 mM) (Peng et al, 1996), and that for activation of eNOS itself (3 ± 5 mM) in pulmonary artery endothelial cells (Su et al, 1997). It would therefore seem likely that the rate limiting step is the concentration of L-arginine delivered to the eNOS enzyme rather than the transport of L-arginine across the membrane, as the most important L-arginine transport mechanism, system y + , has been reported to have an EC 50 greater than 50 mM L-arginine in pulmonary artery endothelial cells (Greene et al, 1993).…”

Section: Concentration Dependence Of Response To L-argininementioning

confidence: 99%

Critical dependence of the NO‐mediated component of cyclic AMP‐induced vasorelaxation on extracellular L‐arginine in pulmonary arteries of the rat

Hucks

Ward

2000

British J Pharmacology

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1 A component of isoprenaline-mediated vasorelaxation in pulmonary arteries is mediated by nitric oxide (NO). We examined the eects of physiological concentrations (4400 mM) of L-arginine on isoprenaline-induced relaxation in rat pulmonary arteries, and following inhibition of L-arginine uptake with L-lysine. In addition, we examined the role of the endothelium, and whether L-arginine aected acetylcholine (ACh)-induced relaxation. 2 Isoprenaline-induced relaxation was potentiated by 400 mM L-arginine in pulmonary arteries; maximum relaxation was increased from 83+4% of initial tone to 94+4% (P50.05). L-lysine (10 mM) not only abolished the potentiation by L-arginine, but suppressed relaxation compared to control (70+4%, P50.05), even in the absence of L-arginine added to the bath. Blockade of NO synthase with 100 mM L-NMMA or removal of the endothelium inhibited isoprenaline-induced relaxation to the same extent as L-lysine, and under these conditions the presence or absence of 400 mM L-arginine made no dierence. L-lysine had no additional eect when applied in combination with L-NMMA. 3 The eect of extracellular L-arginine was concentration dependent, with an apparent EC 50 of *1±7 mM. 4 Relaxation to the membrane permeant cyclic AMP analogue CPT cyclic AMP was also potentiated by L-arginine and inhibited by L-lysine. There was however no dierence in relaxation induced by acetylcholine (ACh) in the presence of L-arginine or L-lysine, and isoprenaline-induced relaxation of mesenteric arteries was unaected by L-arginine or L-lysine. 5 These results strongly suggest that extracellular L-arginine is critically important for development of the NO-and endothelium-dependent component of cyclic AMP-induced vasorelaxation in rat pulmonary arteries, but is not required for ACh-induced relaxation. As the apparent EC 50 for this eect is in the low micromolar range it is likely to be fully activated in vivo, as plasma L-arginine is 4150 mM.

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“…The transport activity of system y ϩ is characterized by high affinity for cationic amino acids, sodium independence, and stimulation of transport by substrate on the opposite (trans) side of the membrane (36). System y ϩ transport activity has previously been detected in large vessel endothelial cells (39,40). Two transporters exhibiting y ϩ system properties were cloned from the mouse and were termed cationic amino acid transporter-1 and -2B (CAT-1 and CAT-2B) (41)(42)(43)(44)(45).…”

mentioning

confidence: 99%

Glucocorticoids Regulate Inducible Nitric Oxide Synthase by Inhibiting Tetrahydrobiopterin Synthesis and L-Arginine Transport

Simmons

Ungureanu-Longrois

Smith

et al. 1996

Journal of Biological Chemistry

160

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The cytokine-inducible isoform of nitric oxide synthase (iNOS or NOS2) plays an important role in the immune response to some pathogens. Within the heart, increased activity of NOS2 in cardiac microvascular endothelial cells (CMEC) also can diminish the contractile function of adjacent cardiac myocytes. Glucocorticoids, which are known to suppress cytokine induction of NOS2 in many cell types, caused only a moderate (approximately 20%) decline in NOS2 protein content and maximal activity measured in homogenates of cytokinetreated CMEC, but almost completely inhibited synthesis of nitrogen oxides (NO x ) by intact cells. To determine whether glucocorticoids were inhibiting cellular NO x production by limiting the availability of NOS co-factors or substrate, the effect of dexamethasone on tetrahydrobiopterin (BH4) and L-arginine availability in cytokinetreated CMEC was examined. Dexamethasone prevented the coordinate induction of GTP cyclohydrolase I with NOS2 after exposure to interleukin-1␤ and interferon-␥ and also the increase in intracellular BH4 content in cytokine-treated CMEC. Addition of BH4 overcame dexamethasone-mediated suppression of nitrite production. Dexamethasone also prevented a cytokinemediated increase in L-arginine uptake into CMEC by suppressing the induction of the high affinity cationic amino acid transporters CAT-1 and CAT-2B and the low affinity CAT-2A transporter. In addition, dexamethasone also inhibited cytokine induction in CMEC of argininosuccinate synthase, the rate-limiting enzyme for the de novo synthesis of arginine from citrulline. Thus, glucocorticoids regulate NO x production following cytokine exposure in cardiac microvascular endothelial cells primarily by limiting BH4 and L-arginine availability.

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Characterization of L-arginine transport by pulmonary artery endothelial cells

Cited by 36 publications

References 0 publications

L-Arginine Transport at the Fetal Side of Human Placenta: Effect of Aspirin in Pregnancy

L-Arginine Transport at the Fetal Side of Human Placenta: Effect of Aspirin in Pregnancy

Critical dependence of the NO‐mediated component of cyclic AMP‐induced vasorelaxation on extracellular L‐arginine in pulmonary arteries of the rat

Glucocorticoids Regulate Inducible Nitric Oxide Synthase by Inhibiting Tetrahydrobiopterin Synthesis and L-Arginine Transport

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