Effects of extracellular ATP on surfactant secretion

• Published in: Annals of the New York Academy of Sciences Vol. 603; p. 64
• Main Author: Rice, W R
• Format: Journal Article
• Language: English
• Published: United States 1990
• Subjects: Adenosine Diphosphate - pharmacology; Adenosine Monophosphate - pharmacology; Adenosine Triphosphate - pharmacology; Animals; Caenorhabditis elegans Proteins; Calcium - metabolism; Carrier Proteins; Cells, Cultured; Choline - metabolism; Lung - cytology; Lung - drug effects; Lung - physiology; Male; Phorbol 12,13-Dibutyrate - metabolism; Phosphatidylcholines - metabolism; Protein Kinase C; Pulmonary Surfactants - metabolism; Rats; Rats, Inbred Strains; Receptors, Drug - metabolism
• ISSN: 0077-8923
• DOI: 10.1111/j.1749-6632.1990.tb37662.x

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.