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Use of phosphodiesterase inhibitors to evaluate their roles in regUlating cyclic nucleotide levels in intact cells. Biochem. J. 266,127-132. 46. , Moncada, S. (1991) Modulation of platelet aggregation by an arginine: nitric oxide pathway. TIPS, 12,87-88. 47. A. (1990) Prostaglandin endoperoxide/thromboxane A2 receptor desensitization. Cross- talk with adenylate cyclase in human platelets. J. BioI. Chern. 265,21670-21675. 48. R. (1988) Endothelium- derived relaxing factor reduces platelet adhesion to bovine endothelial cells.

Pharmacology of nitric oxide formation and action Under physiological conditions, there is little effect of L -Arg administered acutely on the formation of NO by the intact endothelium and by resting platelets [17,18,24]. This may be due to a high plasma and intracellular content of L- Arg which may down- regulate both transport and activation of NO synthase as well as to the presence of arginase, an enzyme which redirects L- Arg towards metabolites of the urea cycle [107-111]. However, transport of L -Arg into cultured endothelial cells which have previously been depleted of this amino acid is up- regulated and, under these circumstances, L- Arg causes the formation of NO [17,112].

Moncada, S. (1987) Nitric oxide accounts for the biological activity of endothelium - derived relaxing factor. Nature 327,524-526. 9. , Moncada, S. (1987) Comparative pharmacology of EDRF and nitric oxide on vascular strips. Eur. J. Pharmacol. 141,445-451. 10. , Moncada, S. (1987) Comparative pharmacology of endothelium - derived relaxing factor, nitric oxide and prostacyclin in platelets. Br. J. Pharmacol. 92,181-187. 11. , Moncada S. (1987) The anti aggregating properties of vascular endothelium: interactions between prostacyc1in and nitric oxide.

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