Gastroduodenal defense.
OBJECTIVE
The gastroduodenum resists mucosal injury despite continuous exposure to concentrated gastric acid. The mucosal barrier consists of a preepithelial mucus HCO3- layer, intercellular tight junctions connecting the epithelial cells, and submucosal acid sensors, prostaglandins, cytokines, enteric nerves and blood flow. In the past year, study of these defensive mechanisms has revealed new insight into the observed sex differences in ulcer prevalence, the protective role of transforming growth factor, the role of serotonin in regulating HCO3- secretion, the role of mechanisms in ulcer healing, the interaction of trefoil factors with the mucus gel, the interaction of glucocorticoids with cyclooxygenase and the characterization of novel, mucosal sparing antiinflammatory agents.


RESULTS
Transforming growth factor, melatonin, serotonin, trefoil factors and H2S all enhance mucosal barrier function or accelerate ulcer healing. Newer coxibs may have safety and advantages over existing compounds. Existing nonsteroidal antiinflammatory drugs may be safer than originally thought.


CONCLUSIONS
The continued elucidation of basic defense mechanisms has led to the development of several new compounds designed to enhance barrier function and repair mechanisms.
Ham
Maggie
M
The David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Kaunitz
Jonathan D
JD
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004386:Duodenum / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008550:Melatonin / Q000502:physiology; D010084:Oxidation-Reduction; D010455:Peptides / Q000276:immunology / Q000502:physiology; D010743:Phospholipids / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D012701:Serotonin / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D016211:Transforming Growth Factor alpha / Q000502:physiology; D000071164:Trefoil Factor-2
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D005938:Glucocorticoids; D010455:Peptides; D010743:Phospholipids; D011758:Pyrroles; D013449:Sulfonamides; D016211:Transforming Growth Factor alpha; D000071164:Trefoil Factor-2; D012701:Serotonin; C514354:apricoxib; D008550:Melatonin