Modulation of the cationic amino acid transport system y+L by surface potential, ouabain and thrombin in human platelets: effects of uremia.
| Autor: | Alves de Sá Siqueira M; Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil., Martins MA, Rodrigues Pereira N, Bandeira Moss M, Santos SF, Mann GE, Mendes-Ribeiro AC, Brunini TM |
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| Jazyk: | angličtina |
| Zdroj: | Nephron. Experimental nephrology [Nephron Exp Nephrol] 2007; Vol. 107 (4), pp. e132-8. Date of Electronic Publication: 2007 Nov 15. |
| DOI: | 10.1159/000111040 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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