Binding of Dipyridamole to Human Platelets and to α₁ Acid Glycoprotein and its Significance for the Inhibition of Adenosine Uptake

The interactions of dipyridamole with α₁ acid glycoprotein of plasma and with human platelets are related to inhibition of adenosine uptake by platelets. Binding studies by equilibrium gel filtration suggested that 1 mol of dipyridamole binds per mol of α₁ acid glycoprotein with a dissociation constant of 1.6 μM. Platelets contain two populations of binding sites, one with high and another with lower affinity for the drug. The binding of dipyridamole to the high-affinity sites follows a Michaelis-Menten binding pattern with a dissociation constant of 0.04 μM. Approximately 2 × 10⁴ dipyridamole molecules are bound at the high-affinity sites of each platelet. The lower affinity sites bind the drug with a dissociation constant of 4 μM. In the presence of α₁ acid glycoprotein of plasma, the binding of dipyridamole to human platelets is inhibited. Correspondingly, the dipyridamole inhibition of adenosine uptake by platelets is reduced 1,000-fold by purified α₁ acid glycoprotein. The binding of dipyridamole to human platelets was found to be essential for its inhibition of adenosine uptake by platelets. Dipyridamole decreases the incorporation of [¹⁴C]adenosine radioactivity in platelet nucleotides and reduces the [¹⁴C]-ATP to [¹⁴C]ADP ratio. Purified α₁ acid glycoprotein reverses these effects of dipyridamole on adenosine metabolism of platelets in a concentration-dependent manner. An equilibrium of dipyridamole binding to α₁ acid glycoprotein and to platelets is proposed.

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