No abstract

Gastric parietal cells in mice present a spectrum of microscopic appearances due mainly to variations in the abundance of the tubular and vesicular component of the cytoplasm and in the size and number of microvilli lining the intracellular canaliculi. Differences in the range of forms among parietal cells of fasting versus fed mice were not especially striking, but cells with very numerous tubules and vesicles were more common after fasting. However, in mice treated with drugs or hormones that induce acid secretion, parietal cells were more uniform in appearance. There was a marked reduction of these cytoplasmic membranes and a concomitant increase in both the number and size of microvilli. Measurements of acid secretion in control animals and in animals treated with acid secretagogues indicated hydrogen ion secretion contemporaneous with depletion of the cytoplasmic tubulovesicular membranes and with increase of the microvilli. In mice with inhibited acid secretion, parietal cells showed an accumulation of cytoplasmic tubules and vesicles and reduction in the numbers of microvilli. Stereological methods were used to quant~tate 10 different parietal cell compartments. Tracer studies with lanthanum did not reveal continuity between the tubules and the plasma membrane. However, there were regions of close apposition between the tubulovesicular membranes and the cell membrane of the canaliculus, and instances where cytoplasmic tubules extended from the cell into the core of enlarged microvilli.

Guinea pig gastric mucosae stripped of their outer muscle layers were studied in Ussing chambers for up to 14 h. Ten minutes after the mucosae were mounted in the chamber, the electrical parameters were low but continued to rise over 90 min until steady-state potential difference (PD), resistance (R), and short-circuit current (Isc) were recorded. Morphological analysis during the first 10 min of the tissue in the chamber revealed gaps in the epithelium due to damaged cells. However, tissues examined after 20 min in the chamber showed little evidence of epithelial discontinuity. Thereafter, the initial rise in the electrical parameters was noted. After steady-state attainment, the lumen was exposed to 1.25 M NaCl for 5 min and then changed back to 150 mM NaCl. Ten minutes after washout and return to control solutions, the PD, R, and Isc had fallen to low values. At 30 min after washout of the NaCl, the PD, R, and Isc began to increase and after 2 h were back to control values. Morphological analysis of mucosae fixed up to 10 min after exposure to 1.25 M NaCl showed extensive damage and exfoliation of surface cells. However, by 30 min the epithelium was restored and had very few discontinuities, which was then followed by the return of the electrical parameters. The conclusions from these studies are 1) guinea pig gastric mucosae exposed to hypertonic NaCl on the luminal side will primarily result in surface epithelial cell destruction with an immediate drop in the transepithelial electrical values; 2) after return to isotonic saline the damaged mucosa can repair itself within minutes, which then allows the reestablishment of the transepithelial electrical parameters by 2 h; and 3) the good viability and reproducibility of this preparation present a suitable mammalian model system for the study of factors of mucosal repair.

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.