Interactions of the ADP Analogs, 2′-0-Methyl ADP and Adenine 9-β-D-Arabinofuranoside 5′-Diphosphate and Catecholamines with Human Platelets

The two analogs 2'0-methyl ADP (Me'ADP) and adenine 9-β-D-arabinofuranoside 5'-diphosphate (A-Ara-DP) are compounds with stereochemical modification in the pentose moiety of ADP. These compounds have been added individually to citrated platelet rich plasma (PRP) and the concentration dependent interaction of each with platelets has been studied turbidimetrically using a dual channel Payton Aggregometer under the following experimental conditions:variable amounts of compound only; variable amounts of compound challenged at 30" or 5' by an aggregation-stimulating ADP concentration; or variable amounts of compound plus aggregation-stimulating concentrations of epinephrine (EPI) or norepinephrine (NOR) added after 30".Data obtained indicate that both compounds induce reversible aggregation at high concentrations, and that neither compound competes effectively with ADP added after 30". Both compounds delay the secondary wave of aggregation when ADP is added after 5'. Both compounds also exhibit mild dose dependent cooperative effects when epinephrine or norepinephrine are added 30" later.The ADP analogs, Me'ADP and A-Ara-DP, exhibit weak interactions with the platelet ADP receptor, indicating the importance of the ribose conformation in this case. The mild cooperative effects for either of these analogs plus EPI or NOR also suggest that the platelet ADP and catecholamine receptors are independent but interacting. Supported by USPHS HL-15425.