Medical Pharmacology Chapter 27:  Gastrointestinal Drugs

• Gastric mucosa and acid secretion

  • Oxidative phosphorylation dependent secretion by parietal cells.

    • Parietal cells: found in mucosal glands of the body and fundus of the stomach.

     

    • Human Parietal Cells

      Hoffmeier (JPogi):  Human Parietal Cells en.wikipedia.org/wiki/Parietal_cell

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      Control of Stomach: Acid Secretion

      Lupin  Diagram summarizing control of stomach acid secretion Antral mucosal endocrine cells (D cells) Enterochromaffin-like cell (ECL-cells) Gastrin secreting cell (G cell) en.wikipedia.org/wiki/Parietal_cell

       

  • Regulation of gastric acid secretion involves many factors (chemical, neural, hormonal)

    • Stimulation:

      1. Gastrin-most potent stimulant

      2. Activation of postganglionic vagal fibers (muscarinic cholinergic parietal cells receptor activation)

      3. Role of histamine:

         • Gastric mucosa contains large amounts of histamine in:

           1. Mast cell cytoplasmic granules

           2. Enterochromaffin-like cells (ECL)

         • H₂ receptor antagonists competitively inhibit histamine action on H₂ receptors, located on:

           1. Gastric parietal cells

           2. Cardiac atrial cells

           3. Uterine smooth muscle cells

         • H₂ receptor antagonists (cimetidine (Tagamet), ranitidine (Zantac), famotidine (Pepcid), nizatidine (Axid)) inhibit:

           1. Basal acid secretion

           2. Secretion in response to feeding, gastrin, histamine, hypoglycemia, or vagal stimulation

         • Histamine is the most important gastric acid secretion stimulant and is released from enterochromaffin-like cells by gastric and cholinergic activity

      4. Basolateral parietal cells membranes contain receptors for:

         • Histamine-- stimulation gastric acid secretion

         • Gastrin-- stimulation gastric acid secretion

         • Acetylcholine-- stimulation gastric acid secretion

         • Prostaglandins --inhibition of gastric acid secretion

         • Somatostatin -- inhibition of gastric acid secretion

          

  • Regulation of Gastric Secretion of Hydrochloric Acid (HCl)

    "Regulation of Gastric Secretion of HCl. The solid arrows indicate stimulation; the dashed arrow indicates inhibition. " courtesy of Robert H. Parsons, Ph.D., Rensselaer Polytechnic Institute, used with permission

Friedman, L. S. and Peterson, W.L. Peptic Ulcer and Related Disorders In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., and Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp. 1597-1616.