Interaction of Human Blood Platelets with the 2′,3′‐Dialdehyde and 2′,3′‐Dialcohol Derivatives of Adenosine 5′‐Diphosphate and Adenosine 5′‐Triphosphate

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Abstract
The 2'',3''-dialdehyde derivative of ADP (oADP) at concentrations approaching the millimolar range induced human blood platelets to undergo the transition from discoid to globular morphology (the shape change) but was incapable of inducing aggregation. When incubated with platelets for 1 min before addition of the agonist, oADP acted as a competitive inhibitor of shape change and aggregation induced by ADP. Under these conditions secretion and aggregation induced by low concentrations of collagen and secretion and secondary aggregation induced by adrenaline [epinephrine], thrombin and vasopressin were also inhibited by this analog. oADP stimulated the rate of primary aggregation induced by adrenaline and caused partial inhibition of primary aggregation induced by thrombin or vasopressin. When longer preincubation times were employed, the extent of inhibition with respect to all agonists, except for high concentrations of collagen, was increased, and the competitive character of the inhibition with respect to ADP was no longer apparent. Incubation of human platelets with the 2'',3''-dialdehyde derivative of ATP (oATP) caused effects similar to those described for oADP except that the analog neither induces platelet shape change, nor stimulates the rate of primary aggregation induced by adrenaline. oATP failed to cause significant inhibition of platelet shape change induced by serotonin. The extent and character of inhibition caused by addition of oATP was not a function of the time of incubation. The 2'',3''-dialcohol derivatives of ADP (orADP and orATP) affected the aggregation properties of human blood platelets in a manner generally resembling those observed for the 2'',3''-dialdehyde analog. orADP was only weakly effective in causing platelet shape change and stimulating the rate of primary aggregatin induced by adrenaline and did not inhibit secretion induced by adrenaline, collage, thrombin and vasopressin. The extent of inhibition by orADP increased only slightly with increased time of incubation. Apparently oADP acts as a partial agonist, and oATP as an antagonist, at the platelet ADP receptor but platelet membrane stabilization also results from interaction with these dialdehyde analogs. Such membrane stabilization does not complicate the interaction of platelets with orADP, which appears to act as a classical antagonist for the ADP receptor.