Inhibition of ADP-Induced Responses in Human Platelets by Agents Elevating the Cyclic AMP Level: Comparison of Aggregation and Shape Change

Summary

The inhibitory effect of cAMP-elevating agents on shape change and aggregation in human platelets was studied to improve the understanding of the sequential relationship between these two responses.

Human platelet-rich plasma was preincubated for 2 min at 37° C with prostaglandin E₁ or adenosine, agents known to elevate the intracellular level of cAMP. Their inhibitory effects on ADP-induced shape change and aggregation were determined both separately and simultaneously. The dose-inhibition patterns for shape change and aggregation were similar for both PGE₁ and adenosine. There was no distinct difference between the inhibitory action of these two inhibitors.

These observations suggest that elevation of the intracellular concentration of cAMP interferes with an early step in the stimulus-response coupling that is common for aggregation and shape change.

Key words

ADP - Aggregation - Cyclic AMP - Inhibition - Platelets - Shape change

• References

• 1 Mills DC B, Smith JB. The influence on platelet aggregation of drugs that affect the accumulation of adenosine-3’,5’-cyclic monophosphate in platelets. Biochem J 1971; 121: 185-196
• 2 Haslam RJ. Interactions of the pharmacological receptors of blood platelets with adenylate cyclase. Ser Haematol 1973; 6: 333-350
• 3 Haslam RJ, Rosson GM. Effects of adenosine on levels of adenosine cyclic-3’,5’-monophosphate in human blood platelets in relation to adenosine incorporation and platelet aggregation. Mol Pharmacol 1975; 11: 528-544
• 4 Haslam RJ. Roles of cyclic nucleotides in platelet function. In: Biochem and Pharmacol, of platelets: Ciba Found Symp 1975; 35: 121-151
• 5 Yamanishi J, Kawahara Y, Fukuzaki H. Effect of cyclic AMP on cytoplasmic free calcium in human platelets stimulated by thrombin: Direct measurement with quin 2. Thromb Res 1983; 32: 183-188
• 6 Feinstein MB, Egan JJ, Sha’afi RI, White J. The cytoplasmic concentration of free calcium in platelets is controlled by stimulators of cyclic AMP production (PGD₂, PGE₁, forskolin). Biochem Biophys Res Comm 1983; 113: 598-604
• 7 Holmsen H, Setkowsky CA, Day HJ. Effects of antimycin and 2- deoxyglucose on adenine nucleotides in human platelets. Biochem J 1974; 144: 385-396
• 8 Shio H, Plasse AM, Ramwell PW. Platelet swelling and prostaglandins. Microvasc Res 1970; 2: 294-301
• 9 Kinlough-Rathbone RL, Packham MA, Mustard JF. The effect of prostaglandin E, on platelet function in vitro and in vivo. Br J Haematol 1970; 19: 559-570
• 10 Born GV R. Observations on the change in shape of blood platelets brought about by adenosine diphosphate. J Physiol 1970; 209: 487-511
• 11 Frojmovic MM, Milton JG, Duchastel A. Microscopic measurements of platelet aggregation reveal a low ADP-dependent process distinct from turbidometrically measured aggregation. J Lab Clin Med 1983; 101: 964-976
• 12 Gear AR L. Rapid reactions of platelets studied by a quenched-flow approach: Aggregation kinetics. J Lab Clin Med 1982; 100: 866-886
• 13 Marguerie GA, Plow EF, Edgington TS. Human platelets possess an inducible and saturable receptor specific for fibrinogen. J Biol Chem 1979; 254: 5357-5363
• 14 Bennett JS, Vilaire G. Exposure of platelet fibrinogen receptors by ADP and epinephrine. J Clin Invest 1979; 64: 1393-1401
• 15 Peerschke EI, Zucker MB, Grant RA, Egan JJ, Johnson MM. Correlation between fibrinogen binding to human platelets and platelet aggregability. Blood 1980; 55: 841-847
• 16 Marguerie GA, Plow EF. The fibrinogen dependent pathway of platelet aggregation. Ann NY Acad Sci 1983; 408: 556-566
• 17 Peerschke EI, Zucker MB. Fibrinogen receptor exposure and aggregation of human blood platelets produced by ADP and chilling. Blood 1981; 57: 663-670