Effects of extracellular ATP on surfactant secretion.

Extracellular ATP is the most potent endogenous stimulus for surfactant phospholipid secretion from alveolar type II cells identified to date. This effect of ATP appears mediated via a P2-purinoceptor because the rank order of agonist potency is ATP greater than ADP greater than AMP = adenosine. Examination of other ATP analogues demonstrates a rank order of agonist potency of ATP = gamma S-ATP greater than AMPPNP greater than AMPPCP greater than AMPCPP for surfactant secretion, consistent with a P2y-purinoceptor mediating this effect. This hypothesis is further supported by experiments with reactive blue 2, which selectively inhibits ATP-stimulated surfactant phospholipid secretion and has been purported as a specific inhibitor at P2y-purinoceptors. Several second messenger systems are activated in the type II cell following agonist binding: intracellular Ca2+ is mobilized, prostaglandin levels increase, and protein kinase C is activated. Of these three second messengers, protein kinase C appears to be the most important for surfactant secretion because inhibition of protein kinase C activation blocks ATP-induced surfactant secretion whereas inhibition of Ca2+ mobilization and prostaglandin production does not affect ATP-induced surfactant secretion.