Guanine nucleotides inhibit agonist‐stimulated arachidonic acid release in both intact and saponin‐permeabilized human platelets

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Abstract
The effects of guanine nucleotides on arachidonic acid (AA) release were studied in intact and saponin‐permeabilized human platelets. While GTP[S] itself caused a stimulation of AA release in permeabilized cells, GTP[S], GDP[S], GTP, ATP and other nucleotides inhibited AA release in response to thrombin and other agonists in intact, as well as permeabilized platelets. Inhibition of agonist‐stimulated AA release by nucleotides was partially attenuated by addition of ADP, and was abolished by prior stimulation of platelets to discharge the ADP‐containing dense granules. These results suggest: (i) that released ADP plays an important contributory role in agonist‐stimulated platelet AA release, and (ii) that guanine nucleotides can modulate platelet activation through an extracellular action which is distinct from their effects on G‐proteins.