The prostacyclin analogues, iloprost and treprostinil are extensively used in 
treating pulmonary hypertension. Their binding profile and corresponding 
biochemical cellular responses on human prostanoid receptors expressed in cell 
lines, have now been compared. Iloprost had high binding affinity for EP1 and IP 
receptors (Ki 1.1 and 3.9 nM, respectively), low affinity for FP, EP3 or EP4 
receptors, and very low affinity for EP2, DP1 or TP receptors. By contrast, 
treprostinil had high affinity for the DP1, EP2 and IP receptors (Ki 4.4, 3.6 
and 32 nM, respectively), low affinity for EP1 and EP4 receptors and even lower 
affinity for EP3, FP and TP receptors. In functional assays, iloprost had 
similar high activity in elevating cyclic AMP levels in cells expressing the 
human IP receptor and stimulating calcium influx in cells expressing EP1 
receptors (EC50 0.37 and 0.3 nM, respectively) with the rank order of activity 
on the other receptors comparable to the binding assays. As with binding 
studies, treprostinil elevated cyclic AMP with a similar high potency in cells 
expressing DP1, IP and EP2 receptors (EC50 0.6, 1.9 and 6.2 nM, respectively), 
but had low activity at the other receptors. Activation of IP, DP1 and EP2 
receptors, as with treprostinil, can all result in vasodilatation of human 
pulmonary arteries. However, activation of EP1 receptors can provoke 
vasoconstriction, and hence may offset the IP-receptor mediated vasodilator 
effects of iloprost. Treprostinil may therefore differ from iloprost in its 
overall beneficial pulmonary vasorelaxant profile and other pharmacological 
actions, especially in diseases where the IP receptor is down-regulated.