The gastric parietal cell is responsible for the secretion of HCl into the lumen of the stomach mainly due to stimulation by histamine via the cAMP pathway. However, the participation of several other receptors and pathways have been discovered to influence both stimulation and inhibition of acid secretion (e.g., cholinergic). Here we examine the role of phosphoinositide 3-kinase (PI3K) in the modulation of acid secretion. Treatment of isolated gastric glands and parietal cells with the PI3K inhibitor, LY294002 (LY), potentiated acid secretion in response to histamine to nearly the maximal secretion obtained with histamine plus phosphodiesterase inhibitors. As cAMP levels were elevated in response to histamine plus LY, but other means of elevating cAMP (e.g., forskolin, dbcAMP) were not influenced by LY, we posited that the effect might require activation of G-protein-coupled histamine H(2) receptors, possibly through the protein kinase B pathway (also known as Akt). Study of downstream effectors of PI3K showed that histaminergic stimulation increased Akt phosphorylation, which in turn was blocked by inhibition of PI3K. Expression studies showed that high expression of active Akt decreased acid secretion, whereas dominant-negative Akt increased acid secretion. Taken together, these data suggest stimulation with histamine increases the activity of PI3K leading to increased activity of Akt and decreased levels of cAMP in the parietal cell.
The metaphase II mouse egg is polarized. One domain, known as the microvillar domain, supports sperm binding and fusion. The other domain, known as the amicrovillar domain, has an equally important job: sequestration of the metaphase II spindle. This image is a projection created from a series of optical sections from approximately the equator of the egg to the pole where the metaphase II spindle is localized. It has long been appreciated that an actin-rich cap develops during meiotic maturation in this region over the metaphase II spindle (e.g., Dev. .Highlighted in this image is a myosin-II-enriched microdomain (green, detected by an antibody to the active, phosphorylated form of the myosin-II regulatory light chain) that surrounds the metaphase II spindle (DNA is shown in blue; -tubulin in red). This domain also exhibits increased tension as compared to the rest of the egg (Mol. Biol. Cell 21:3182-3192). This physical attribute adds a new perspective to cell polarity in the metaphase II egg -the egg has mechanical polarity, in addition to the polarized localizations of various proteins and the differences in functions of the egg membrane and cortex between these two domains.The molecular and mechanical features of this cell polarity in the egg appear sequester the spindle, serving to isolate the spindle from the rest of the egg and facilitating spindle function and the asymmetric cytokinesis that creates the second polar body upon fertilization (Mol. Biol. Cell 21:3182-3192).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.