Modulation of the cationic amino acid transport system y+L by surface potential, ouabain and thrombin in human platelets: effects of uremia.

Abstract

BACKGROUND:

Nitric oxide (NO), a key endogenous mediator involved in the maintenance of platelet function, is synthesized from the amino acid L-arginine. We have shown that L-arginine transport in platelets is rate-limiting for NO synthesis. A disturbance in the L-arginine-NO pathway in platelets was previously described in chronic renal failure (CRF) patients.

METHODS:

Detailed kinetic studies were performed in platelets from controls (n = 60) and hemodialysis patients (n = 26).

RESULTS:

The transport of L-arginine in platelets is mediated via system y+L, which is competitively inhibited by L-leucine in the presence of Na+ and by the irreversible inhibitor pCMB. In platelets, system y+L is markedly stimulated by an Na+/K+-ATPase inhibitor, ouabain, and by changes in surface potential, while it is downregulated by intraplatelet amino acid depletion (zero-trans) and by thrombin. In CRF patients, activation of L-arginine transport was limited to well-nourished patients compared to malnourished patients and controls, where it was reduced and did not differ significantly among the groups under zero-trans conditions.

CONCLUSION:

Our results provide the first evidence that system y+L in platelets is modulated by zero-trans conditions, surface potential, thrombin and intraplatelet Na+ concentration. Our findings suggest that enhanced transport in CRF involves increased L-arginine exchange with intraplatelet neutral amino acids.

• Authors: Mariana Alves de Sá Siqueira, Marcela Anjos Martins, Natália Rodrigues Pereira, Monique Bandeira Moss, Sérgio F F Santos, Giovanni E Mann, Antônio C Mendes-Ribeiro, Tatiana M C Brunini
• Journal: Nephron. Experimental nephrology (Nephron Exp Nephrol) Vol. 107 Issue 4 Pg. e132-8 ( 2007) ISSN: 1660-2129 [Electronic] Switzerland
• PMID: 18025792 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Transport System y+L
• Enzyme Inhibitors
• Hemostatics
• Lipopolysaccharides
• Tumor Necrosis Factor-alpha
• Tritium
• Nitric Oxide
• Ouabain
• Arginine
• Sodium
• Thrombin
• Glucose

Topics

• Adult
• Amino Acid Transport System y+L (metabolism)
• Arginine (pharmacokinetics)
• Biological Transport (drug effects, physiology)
• Blood Platelets (drug effects, metabolism)
• Enzyme Inhibitors (pharmacology)
• Glucose (pharmacology)
• Hemostatics (pharmacology)
• Humans
• In Vitro Techniques
• Kidney Failure, Chronic (metabolism)
• Lipopolysaccharides (pharmacology)
• Membrane Potentials
• Nitric Oxide (metabolism)
• Ouabain (pharmacology)
• Sodium (metabolism)
• Thrombin (pharmacology)
• Tritium
• Tumor Necrosis Factor-alpha (pharmacology)
• Uremia (metabolism)