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The results of the present study show that human platelets take up L-arginine by two transport systems which are compatible with the systems y + and y + L. These Na + -independent transporters have been distinguished by treat-ing platelets with N-ethylmaleimide that blocks selectively systemy + .Systemy + , that accounts for 30–40%of the total transport, is characterized by low affinity forL-arginine, is unaffected byL-leucine, is sensitive to changes of membrane potential and totrans-stimulation. . | Eur. J. Biochem. 270 2005-2012 2003 FEBS 2003 doi 10.1046 j.1432-1033.2003.03572.x Transport of L-arginine and nitric oxide formation in human platelets Maria G. Signorello Raffaele Pascale and Giuliana Leoncini Dipartimento di Medicina Sperimentale sezione Biochimica Universitci di Genova Italy The results of the present study show that human platelets take up L-arginine by two transport systems which are compatible with the systems y and y L. These Na -independent transporters have been distinguished by treating platelets with N-ethylmaleimide that blocks selectively system y .Systemy that accounts for 30-40 of the total transport is characterized by low affinity for L-arginine is unaffected by L-leucine is sensitive to changes of membrane potential and to trans-stimulation. The other component of L-arginine transport identified with the system y L approximately 60-70 of the total flux shows high affinity for L-arginine is insensitive to N-ethylmaleimide treatment unaffected by changes in membrane potential sensitive to trans-stimulation and inhibited by L-leucine in the presence ofNa . Moreover a strict correlation between L-arginine transport and nitric oxide NO production in whole cells was found. N-ethylmaleimide and L-leucine decreased NO production as well as cGMP elevation and the effect on NO and cGMP were closely related. It is likely that the L-arginine transport systems y and y L are both involved in supplying substrate for NO production and regulation in human platelets. Keywords L-arginine nitric oxide platelets transport. The cationic amino acid L-arginine is the main source for the synthesis of nitric oxide NO in many cell types 1 . NO exerts different functions in the regulation of vascular tone and blood pressure and in neurotransmission in central nervous system 2 . One of the most relevant functions of NO is the inhibition of platelet aggregation 3 4 . The regulation of platelet activation is crucial to prevent platelet aggregation thrombus .