[Signal transduction and intracellular recruitment of gastric proton pump in the parietal cell].
The parietal cell has three types of activating receptors for acid secretion on its basolateral membrane, i.e., histamine H2, acetylcholine M3, and gastrin CCKB. Activation of acid secretion is achieved by two concomitant functional changes namely: (i) tubulovesicles fuse with the apical secretory membrane, thus recruiting functional pumps to the expanded microvillar surface, and (ii) the apical membrane acquires a permeability to KCl. The major path for parietal cell stimulation is via H2-receptor-mediated adenylate cyclase and elevation of cAMP to activate protein kinase A (PKA), which phosphorylates key effector proteins, e.g., ezrin, a membrane-cytoskeletal linker, apical Cl- or K(+)-channels. Ca2+ is liberated from intracellular stores by IP3, which in turn is the result of M3-, CCKB-, or possibly H2-coupled activation of phospholipase C. The resulting protein kinase C activation may have both inhibitory and excitatory roles. Elevated Ca2+ activates calmodulin-dependent kinases, e.g., calmodulin kinase II and myosin light chain kinase, that could promote vesicular motor activity. Ezrin is considered to play a main role in the vesicular transport system of the parietal cell. The regulation might be conducted through the phosphorylation of the molecule to modify its property to interact with the cytoskeletal components, membranes or membrane proteins.
Urushidani
T
T
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
Nagao
T
T
D000818:Animals; D002118:Calcium / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D003598:Cytoskeletal Proteins; D005744:Gastric Acid / Q000378:metabolism*; D010295:Parietal Cells, Gastric / Q000378:metabolism*; D010750:Phosphoproteins / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D017494:Proton Pumps / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000099149:Ezrin
D002118:Calcium; D017868:Cyclic AMP-Dependent Protein Kinases; D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D011493:Protein Kinase C; D017494:Proton Pumps; D000099149:Ezrin