Guanine nucleotides inhibit agonist-stimulated arachidonic acid release in both intact and saponin-permeabilized human platelets.
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.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003094:Collagen / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D012265:Ribonucleotides / Q000494:pharmacology; D012503:Saponins; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000502:physiology; D014357:Trypsin / Q000494:pharmacology
D001095:Arachidonic Acids; D006150:Guanine Nucleotides; D012265:Ribonucleotides; D012503:Saponins; D016718:Arachidonic Acid; D003094:Collagen; D014357:Trypsin; D013917:Thrombin