In frog fundic mucosae mounted in Ussing chambers, exposure to luminal 1 M NaCl for 10 min caused a sharp immediate decrease in potential difference, resistance, short circuit current, and acid secretion, but within 4-6 h these readings had returned toward control values. After initial severe destruction of surface epithelial cells, gradual morphologic restitution occurred within 4-6 h. A Ca2+-free nutrient solution and 4 mM ethylenediaminetetraacetic acid administered after injury prevented both physiologic and morphologic restitution. A Ca2+-free nutrient solution administered alone after injury prevented physiologic recovery, but although narrow gaps and lack of tight junctions were found between some cells, there was near-complete epithelial cell coverage. The addition of 2 mM Ca2+ to these tissues 3 h after injury effected rapid recovery of electrophysiologic parameters and a complete closure of the intercellular spaces. Cytochalasin B (3 X 10(-3) M nutrient) prevented physiologic recovery and mucosal restitution. Neither cycloheximide nor colchicine had any effect on the normal process of restitution. Autoradiography of [3H]thymidine incorporation showed no increase in labeling within 4 h of hyperosmolar injury. We conclude that adequate Ca2+ is required for complete restitution of gastric mucosa after hyperosmolar injury, and that restitution occurs by migration of persisting viable gastric pit cells.
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