Summary
Forskolin, a plant (Coleus forskohlii) diterpene, inhibits ADP- induced (human: IC50, 2.3±1.0 μ;M; rat: IC50, 1.2±0.5 μM) and collagen-induced (human: IC50, 2.4±1.2 μM; rat: 0.6±0.2 μM) platelet aggregation in human and rat platelet-rich
plasma (PRP). Human blood levels of adenosine (Ado) are low (100-300 nM) as compared
to levels in rat plasma (7.55 ± 0.51 μM). Ado is a natural antiplatelet and vasodilatory
agent produced by vascular endothelium, heart and other body tissues. If the plasma
Ado is degraded by pretreatment of PRP with adenosine deaminase (ADA), forskolin inhibition
on platelet aggregation is reduced by 2-4 fold both in human and rat blood. On the
other hand, if the physiological steady state levels of Ado are maintained by collecting
the blood in the presence of the inhibitors of ADA (2’-deoxycoformycin, dCF, 5 μM)
and Ado uptake (dipyridamole, 10 μM or dilazep, 2 μM), forskolin inhibition (IC50, 3.2 μM) on platelet aggregation in human PRP is potentiated by 20-40 fold (IC50, 0.075-0.15 μM). Similar potentiated forskolin effect (IC50, 0.53 μM) is seen if the ADA-treated human PRP is replenished with a low level of
Ado (50 nM) after ADA inactivation by dCF and Ado-uptake blockade by dilazep. If the
plasma is replenished with a higher concentration of Ado (300 nM), greater potentiation
is seen (IC50, 0.23 μM). Forskolin is 2-4 fold more inhibitory in rat PRP than in human PRP, partially
due to the presence of higher levels of Ado in the rat plasma. These studies demonstrate
an important role of plasma Ado in the antiplatelet activity of forskolin and this
effect can be greatly potentiated by the clinically used drugs, dipyridamole and dilazep.
Key words
Platelet - Forskolin - Adenosine - Dipyridamole - Dilazep