Prostanoid inhibition of canine parietal cells

• Published in: The American journal of medicine Vol. 81; no. 2; pp. 5 - 11
• Main Authors: Soll, Andrew H., Chen, Monica C.Y., Amirian, Deborah A., Toomey, Mary, Alvarez, Robert
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.08.1986
• Subjects: 1-Methyl-3-isobutylxanthine - pharmacology; Adenylyl Cyclase Inhibitors; Adenylyl Cyclases - metabolism; Aminopyrine - metabolism; Animals; Carbachol - pharmacology; Cells, Cultured; Colforsin - pharmacology; Cyclic AMP - antagonists & inhibitors; Cyclic AMP - biosynthesis; Dinoprostone; Dogs; Enprostil; Histamine - pharmacology; Parietal Cells, Gastric - drug effects; Parietal Cells, Gastric - enzymology; Parietal Cells, Gastric - metabolism; Prostaglandins E - pharmacology; Prostaglandins E, Synthetic - pharmacology; Stimulation, Chemical
• ISSN: 0002-9343; 1555-7162
• DOI: 10.1016/S0002-9343(86)80003-1

Cellular mechanisms underlying the anti-secretory actions of the prostaglandin E 2 analogue enprostil were studied using enzyme-dispersed, elutriator-enriched canine parietal cells and the accumulation of the weak base 14C-labeled aminopyrine as a functional index. Enprostil inhibited the accumulation of aminopyrine stimulated by histamine and the phosphodiesterase inhibitor isobutylmethyl, but not by carbachol, gastrin, or dibutyryl cyclic adenosine monophosphate. Inhibition by enprostil was dose-dependent (0.1 nM to 1 μM), with maximal inhibition ranging from 65 to 95 percent. Over the same concentration range, enprostil inhibited the histamine-stimulated generation of cyclic adenosine monophosphate. This selective inhibition of histamine activation of parietal cell function was comparable to that found for prostaglandin E 2. Forskolin, a diterpene that directly activates the catalytic subunit of adenylate cyclase, was also markedly inhibited by nanomolar concentrations of prostaglandin E 2 and enprostil. We conclude that at least a component of the secretory inhibition by enprostil reflects direct interference with histamine stimulation of parietal cell adenylate cyclase.