1 / 29

1.-Architecture of the gastric gland

Gastric Secretion. 1.-Architecture of the gastric gland. 2.- The unique H + /K + ATPase. 3.-Acid secretion homeostasis. Readings :

redell
Download Presentation

1.-Architecture of the gastric gland

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Gastric Secretion 1.-Architecture of the gastric gland 2.- The unique H+/K+ ATPase 3.-Acid secretion homeostasis Readings: 1.-Wallmark B, Larsson H, Humble L. (1985) The relationship between gastric acid secretion and gastric H+,K+-ATPase activity. J Biol Chem. 1985 Nov 5;260(25):13681-4. 2.- Shull GE, Lingrel JB. (1986) Molecular cloning of the rat stomach (H+ + K+)-ATPase. J Biol Chem. 1986 Dec 25;261(36):16788-91. 3.-Anthony M. Paradiso, Roger Y. Tsien & Terry E. Machen (1987) Digital image processing of intracellular pH in gastric oxyntic and chief cells. Nature 325, 447 – 450.

  2. Keywords: Chief cells, Parietal cells, Goblet cells Tubulovesicular network Cymetidine, Omeprazole H+/K+ ATPase Carbonic Anhydrase Chloride bicarbonate exchanger Na+/H+ exchanger

  3. The simplest possible gland is a single cell or cluster of cells in an epithelium, secreting onto the surface (i.e., the mucus secreting goblet cell). Features common to all epithelia: a continuous sheet of cells so that nothing can go in or out of the body without being monitored. Cells show polarity, where the morphology and properties of the membrane facing the inside or the outside of the body, are different. Extensive cell-to-cell contacts called tight junctions (zonula occludens) provide the means of holding the cells together and eliminate the extracellular space (so that nothing can leak between the cells). Finally, in an epithelia, one can always find a basal lamina; a mesh of collagen fibers over which the epithelial cells rests.

  4. This gland consists of an invaginated epithelium of secretory cells lining a blind cavity called acinus. The acinus connects to a small duct that, in turn, along with other acini (not shown), connects to a larger duct that empties at some point of the digestive canal. The epithelial cells that form the acinus (acinar cells) have a characteristic pyramidal shape. The acinar cells have an apical membrane, which faces the lumen (the lumen is the cavity of any hollow organ or tube) and is the secretory surface of the cell. We also have a basal membrane facing the basal lamina and is the place where water and solutes are exchanged between the plasma and the acinar cells. The various substances secreted by the acinar cells comprise the primary secretions, which are subsequently modified by secretions of the duct cells, this is called secondary modifications.

  5. Types of Glands

  6. pH=-Log [H+] The gastric gland generates a fluid mixture composed of mucus, pepsinogen and an electrolytic solution composed of H+ (145 mM), Cl- (155 mM) and K (10 mM). Note that the pH of the gastric juice is less than 1; this means that there is a H+ gradient of about six orders of magnitude between the plasma and the lumen of the gastric gland.

  7. Two other cell types coexist with the parietal and gastric mast cells. These are the chief cells which secrete pepsinogen (a precursor of pepsin) and the ubiquitous goblet cell that secretes mucus, also by exocytosis. The morphology of these cells is shown below. A striking feature of the goblet cells is that their secretory granules are so tightly packed that their membranes touch over extensive regions.

  8. Activation of the pepsinogens to pepsins. At pH values from 5 to 3, pepsinogens spontaneously activate to pepsins by the removal of an N-terminal "activation peptide." This spontaneous activation is even faster at pH values that are below 3. The newly formed pepsins themselves-which are active only at pH values below 3.5-also can catalyze the activation of pepsinogens.

  9. Morphological transformation of the parietal cell Resting Stimulated apical apical basal basal

  10. The Ussing chamber Can be used to study sodium transport by frog skin!

  11. Experimental demonstration of the change in morphology of the gastric gland upon stimulation Ra Rb Ca Cb Equivalent circuit for a gastric gland mounted on a Ussing chamber. Ra and Rb represent the apical and basal membrane resistance, Ca and Cb are the apical and basal membrane capacitances, respectively. Rs represents the series resistance associated with the bathing saline. Upon stimulation with histamine, Ra decreased by a factor of 5 and Ca increased 10 times whereas Rb and Cb remained constant. These results are in good agreement with a large increase in apical surface area upon stimulation.

  12. Morphological transformation of the parietal cell Resting Stimulated apical apical basal basal

  13. Discovery of the H+/K+ ATPase

  14. Vesicular membrane potential for various K+ gradients of K+in/K+out. Both the vesicles from resting (a) and stimulated (b) gastric mucosa show a similar dependence of the vesicular membrane potential, implying that both types of vesicles are equally permeable to K+. (c) plots the vesicular potential versus the log of the Cl- concentration ratio and shows that only the vesicles from the stimulated gastric gland, respond to Cl- gradients. These results imply that there is a new Cl- conductance activated in the stimulated vesicular fraction. We conclude that there are separate K+ and Cl- pathways and that stimulation of the gland leads to the activation of a Cl- conductance in the secretory membrane of the parietal cell.

  15. In 1985, B. Wallmark used the new drug omeprazole to demonstrate that the H+/K+ enzyme was responsible for acid secretion in the gastric gland. [omeprazole]

  16. Acid secretion by parietal cells. When the parietal cell is stimulated, H-K pumps (fueled by ATP hydrolysis) extrude H+ into the lumen of the gastric gland in exchange for K+. The K+ recycles back into the lumen via K+ channels. Cl­ exits through channels in the luminal membrane, completing the net process of HCl secretion. The H+ needed by the H-K pump is provided by the entry of CO2 and H2O, which are converted to H+ and HCO­3 by carbonic anhydrase. The HCO­3 exits across the basolateral membrane via the Cl-HCO3 exchanger. ATP, adenosine triphosphate.

  17. The direct and indirect actions of the three acid secretagogues: acetylcholine, gastrin, and histamine. ACh, acetylcholine; CCKb, cholecystokinin B; ECL, enterochromaffin-like; ENS, enteric nervous system.

  18. Diffusion barrier in the surface of the gastric mucosa. A, The mucus secreted by the surface cells serves two functions. First, it acts as a diffusion barrier for H+ and also pepsins. Second, the mucus layer traps a relatively alkaline solution of HCO­3. This HCO­3 titrates any H+ that diffuses into the gel layer from the stomach lumen. The alkaline layer also inactivates any pepsin that penetrates into the mucus. B, If H+ penetrates into the gastric epithelium, it damages mast cells, which release histamine and other agents, setting up an inflammatory response. If the insult is mild, the ensuing increase in blood flow can promote the production of both mucus and HCO­3 by the mucus cells. If the insult is more severe, the inflammatory response leads to a decrease in blood flow and thus to cell injury.

  19. Receptors and signal-transduction pathways in the parietal cell. The parietal cell has separate receptors for three acid secretagogues. Acetylcholine (ACh) and gastrin each bind to specific receptors (M3 and CCKb, respectively) that are coupled to the G protein Gaq. The result is activation of phospholipase C (PLC), which ultimately leads to the activation of protein kinase C (PKC) and the release of Ca2+. The histamine binds to an H2 receptor, coupled through Gas to adenylyl cyclase (AC). The result is production of cAMP and activation of PKA. Two inhibitors of acid secretion also act directly on the parietal cell. Somatostatin and prostaglandins bind to separate receptors that are linked to Gai. These agents thus oppose the actions of histamine. cAMP, cyclic adenosine monophosphate; CCKb, cholecystokinin B; DAG, diacylglycerol; ER, endoplasmic reticulum; PIP2, phosphatidyl inositol 4,5-biphosphate.

  20. The pulse-chase experiments of Palade defined the secretory pathway Movement of newly synthesized proteins through the secretory pathway. The cell model at the top illustrates the vectoral movement of nascent proteins through the compartments of the secretory pathway. The four records in the graph show the time course of secretory proteins moving through these compartments. To radioactively label newly synthesized proteins, George Palade briefly pulsed the pancreatic acinar cells with 3H-labeled amino acids. At specific times after the pulse, tissues were fixed, and the distribution of the radioactive amino acid was determined using autoradiography. Each of the four records shows the number of radiographic grains-as a fraction of all of the grains-found in each compartment at various times after the pulse. ER, endoplasmic reticulum.

  21. Flow dependence of the electrolyte composition of pancreatic fluid. Note that as the rate at which fluids flow out of the pancreas increases, the composition changes replacing Cl- by HCO-3 in order to neutralize the acid from the stomach and allow the digestive enzymes to work.

More Related