[Studies on the mechanism of restraint-induced gastric ulcer--with special reference to mucosal ischemia and gastric secretion].
Rat gastric mucosal blood flow, hydrochloric acid (HC1) secretion, and morphological changes of parietal cells were studied by light and electron microscopy using histochemical techniques. Mucosal blood flow of restrained rats was remarkably decreased compared with that of control rats, whereas the acetylcholinesterase activity, demonstrated by the method of Karnovsky and Roots, was significantly increased especially near the ulcer. In contrast, the differences in volume, acidity and acid output of gastric juice were not significant between control and restrained rats. Hypersecretion of HC1 induced by a parasympathetic stimulant, bethanechol, was inhibited by blood loss or infusion of cytochalasin B, an actin depolymerizing agent. 14C-aminopyrine accumulation in the primary cultured parietal cells was decreased by the treatment with hypoxia and cytochalasin B. These treatments also prevented the increase of 14C-aminopyrine accumulation induced by bethanechol. Actin filaments were evident in the cytoplasm of the parietal cells, particularly around the intracellular canaliculi and beneath the plasma membrane using the FITC-labeled phalloidin reaction and transmission electron microscopic observations of uranyl acetate block stained preparations following heavy meromyosin decorations. Ultrastructural studies of the parietal cells in restrained rats revealed that intracellular canaliculi were dilated with loss of microvilli. Actin filaments were noted to be disassembled, and granular with focal aggregation of actin filaments. Hypoxic vacuoles were also found in the cytoplasm. Treatments with blood loss and cytochalasin B infusion in the in vivo model, and hypoxia and cytochalasin B in the in vitro model, resulted in the similar changes. These observations indicate that actin filaments in the parietal cells of restrained rats may be depolymerized by ischemia. As the result, HC1 secretion would not be enhanced even if the parasympathetic nerves are excessively stimulated in the gastric mucosa. Thus, disturbances of the gastric mucosal microcirculation are considered to be important in the pathogenesis of the stress-induced gastric ulcer.
Komatsu
H
H
Department of Internal Medicine, School of Medicine, Keio University.
D000199:Actins / Q000378:metabolism; D000818:Animals; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000098:blood supply* / Q000378:metabolism; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D010295:Parietal Cells, Gastric / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D013312:Stress, Physiological / Q000503:physiopathology*
D000199:Actins