Cooperativity of E‐prostanoid receptor subtypes in regulating signaling and growth inhibition in human airway smooth muscle

What is it about?

The therapeutic potential of targeting E prostanoid (EP) receptors has been limited to date due to the lack of drugs capable of specifically targeting each of the 4 EP receptors (EP1, EP2, EP3, and EP4). Drugs that activate EP2 and EP4 receptors in airway smooth muscle (ASM) have the potential to be asthma therapeutics, perhaps being more effective than beta-agonists. Here we characterize the properties of specific agonists of the EP2 and EP4 receptors using both artificial cell systems and primary human airway smooth cells. Our findings demonstrate the specificity of drugs for EP2 and EP4 receptors, and demonstrate that each can promote therapeutic signaling in ASM. Importantly, when EP2 and EP4 agonists are used in combination they can be shown to regulate ASM functions in a manner superior to that of beta-agonists. These studies represent important pre-clinical evidence that EP2/EP4 receptor agonists may be efficacious asthma therapeutics, capable of addressing the needs of asthmatics, 50% of which lack adequate disease control.

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