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Increased nitric oxide synthesis in uraemic platelets is dependent on L-arginine transport via system y(+)L.
Pflugers Arch. 2003 Feb; 445(5):547-50.PA

Abstract

Bleeding tendency in uraemic patients seems to be related to alterations in the activity of the L-arginine-nitric oxide (NO) signalling pathway in platelets. We have reported previously that L-arginine influx into human platelets is mediated by the high-affinity cationic amino acid transport system y(+)L. In the present study we examined the dependency of nitric oxide synthase (NOS) activity on L-arginine transport in platelets isolated from healthy controls and uraemic patients on haemodialysis. We investigated basal and ADP-stimulated NOS activity, as reflected by the conversion of L-[(3)H]arginine to L-[(3)H]citrulline, in platelets obtained from healthy controls and uraemic patients on haemodialysis. To determine whether NOS activity depended on L-arginine transport, we analysed the effects of competitive inhibitors of L-arginine transport via system y(+)L on NOS activity. Basal NOS activity was increased from 0.21+/-0.06 to 0.7+/-0.2 pmol/10(8) platelets (n=9, P<0.05) in uraemic patients. Stimulation by ADP (10 micro M) significantly increased NOS activity (inhibitable by L-NAME) in control platelets (252%) but failed to increase further the elevated NOS activity in uraemic platelets. Homocysteine and L-leucine, competitive inhibitors of system y(+)L, markedly inhibited NOS activity in uraemic platelets. These observations indicate that platelets from uraemic patients on haemodialysis generate more NO than control platelets and that entry of L-arginine via system y(+)L is most likely rate-limiting for platelet NO production in chronic renal failure.

Authors+Show Affiliations

Departamento de Farmacologia e Psicobiologia, Instituto de Biologia, Av. 28 de Setembro 87, CEP 20551-030, Rio de Janeiro, Brazil. cribeiro@physiol.ox.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12634924

Citation

Brunini, T M C., et al. "Increased Nitric Oxide Synthesis in Uraemic Platelets Is Dependent On L-arginine Transport Via System Y(+)L." Pflugers Archiv : European Journal of Physiology, vol. 445, no. 5, 2003, pp. 547-50.
Brunini TM, Yaqoob MM, Novaes Malagris LE, et al. Increased nitric oxide synthesis in uraemic platelets is dependent on L-arginine transport via system y(+)L. Pflugers Arch. 2003;445(5):547-50.
Brunini, T. M., Yaqoob, M. M., Novaes Malagris, L. E., Ellory, J. C., Mann, G. E., & Mendes Ribeiro, A. C. (2003). Increased nitric oxide synthesis in uraemic platelets is dependent on L-arginine transport via system y(+)L. Pflugers Archiv : European Journal of Physiology, 445(5), 547-50.
Brunini TM, et al. Increased Nitric Oxide Synthesis in Uraemic Platelets Is Dependent On L-arginine Transport Via System Y(+)L. Pflugers Arch. 2003;445(5):547-50. PubMed PMID: 12634924.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased nitric oxide synthesis in uraemic platelets is dependent on L-arginine transport via system y(+)L. AU - Brunini,T M C, AU - Yaqoob,M M, AU - Novaes Malagris,L E, AU - Ellory,J C, AU - Mann,G E, AU - Mendes Ribeiro,A C, Y1 - 2002/11/09/ PY - 2002/07/15/received PY - 2002/10/04/revised PY - 2002/10/15/accepted PY - 2003/3/14/pubmed PY - 2003/10/15/medline PY - 2003/3/14/entrez SP - 547 EP - 50 JF - Pflugers Archiv : European journal of physiology JO - Pflugers Arch VL - 445 IS - 5 N2 - Bleeding tendency in uraemic patients seems to be related to alterations in the activity of the L-arginine-nitric oxide (NO) signalling pathway in platelets. We have reported previously that L-arginine influx into human platelets is mediated by the high-affinity cationic amino acid transport system y(+)L. In the present study we examined the dependency of nitric oxide synthase (NOS) activity on L-arginine transport in platelets isolated from healthy controls and uraemic patients on haemodialysis. We investigated basal and ADP-stimulated NOS activity, as reflected by the conversion of L-[(3)H]arginine to L-[(3)H]citrulline, in platelets obtained from healthy controls and uraemic patients on haemodialysis. To determine whether NOS activity depended on L-arginine transport, we analysed the effects of competitive inhibitors of L-arginine transport via system y(+)L on NOS activity. Basal NOS activity was increased from 0.21+/-0.06 to 0.7+/-0.2 pmol/10(8) platelets (n=9, P<0.05) in uraemic patients. Stimulation by ADP (10 micro M) significantly increased NOS activity (inhibitable by L-NAME) in control platelets (252%) but failed to increase further the elevated NOS activity in uraemic platelets. Homocysteine and L-leucine, competitive inhibitors of system y(+)L, markedly inhibited NOS activity in uraemic platelets. These observations indicate that platelets from uraemic patients on haemodialysis generate more NO than control platelets and that entry of L-arginine via system y(+)L is most likely rate-limiting for platelet NO production in chronic renal failure. SN - 0031-6768 UR - https://www.unboundmedicine.com/medline/citation/12634924/Increased_nitric_oxide_synthesis_in_uraemic_platelets_is_dependent_on_L_arginine_transport_via_system_y_+_L_ DB - PRIME DP - Unbound Medicine ER -