Regulation of secretory processes in parietal cells in the different stomach pathologies

This review deals with the analysis of the modern literature concerning molecular mechanisms of secretory activity of gastric mucosa cells and their importance during development of different pathologies. Gastric acid secretion is regulated by paracrine, endocrine and neural systems. The result of these systems functioning at the molecular level is signal transduction pathways activation by histamine, acetylcholine, gastrin and other mediators. Coupling of these agents with specific receptors located on the basolateral plasma membrane of parietal cells modulates acid secretion. It was shown that protein phosphorylation enzymes play the significant role in realization of functional and proliferative activity of the stomach secretory cells in physiological and pathological states. The key role of tyrosine protein kinases associated with growth factors is considered, which take part in regulation of acid secretion, have trophic influence on mucosa cells, protect it from acute injuries, stimulate cell proliferation and accelerate ulcer healing.     

Ultrastructural localisation of carbonic anhydrase in rat stomach parietal cells

Summary Carbonic anhydrase (CA) was shown in rat gastric parietal cells using the optical and electron microscopes. CA activity resulted in an electron-dense precipitate of cobalt sulphide following incubation on Häusler's medium (Häusler, 1958). The cobalt sulphide deposit was found on the outer surface of the microvilli lining the canaliculi of the parietal cell. No such localisation was found after incubation with acetazolamide, a specific inhibitor of CA activity.     

Morphofunctional state of the stomach in rats with hyposalivation

Hypoptyalism and deficiency of physiologically active saliva substances induced by it cause some essential changes in the morphofunctional state of the stomach mucosa, ultrastructure of the gastrin-producing cells and gastrin quantity in blood that testifies to the disturbance of the neurohumoral stomach regulation.     

Morphofunctional changes in the myocardium after extensive bilateral resection of the lungs

In the experiment, performed on 89 dogs, after 67-75% resection of the lungs, functional morphology of the myocardium has been studied by means of histological, electron microscopical and morphometrical methods. Bilateral extensive resections of the lungs are accompanied with hypertrophy of the cardiac muscle, that is revealed at all the levels of its structural organization. Simultaneously, the hypertrophy develops against the background of dystrophic and destructive changes of the myocardium, their depth and extensiveness correlate with duration of the postoperative observations. If an extrapulmonary anastomosis is formed between the inferior lobular pulmonary artery and the corresponding vein before the resection of 67-75% of the lungs, it eliminates the acute overloading of the right ventricle, makes better conditions for development of compensatory-adaptive processes in the myocardium, prevents advancement of the cardio-pulmonary deficiency during the postoperative period.     

Cell population kinetics of zymogen and parietal cells in the stomach of mice

Summary With autoradiography after labelling with tritiated thymidine, the kinetics of zymogen and parietal cells were studied in the gastric mucosa of mice. After one intraperitoneal injection of the DNA precursor, zymogen cells in the DNA synthesis phase were clearly identified on autoradiograms, whereas no parietal cells were seen to synthesize DNA.In another group of mice, multiple injections were used in order to obtain a greater number of labelled cells. Following the latter procedure, analysis of grain count distributions over labelled zymogen cells and of labelling indices allowed detection of two subsequent zymogen cell divisions within an interval of approximately two months. This indicates that the cell turnover of zymogen cells is at least partly assured by their own mitotic activity.By contrast, parietal cells showed no evidence of cell division, but appeared to be derived through differentiation from other cells in the neck area of the gland. Analysis of spatial distribution of the labelled parietal cells in the glandular tube indicated that, in time, most newly formed parietal cells undergo a slow migration directed downwards to the bottom of the fundic glands.These results clearly show that the zymogen and the parietal cell population of the fundic glands have a different kinetic behaviour.This work was supported by a grant of the Nationaal Fonds voor Wetenschappelijk Onderzoek.     

Morphofunctional characteristics of the endocrine cells of the stomach following administration of hydrocortisone and L-thyroxine

Electron microscopy with application of specific fluorescent histochemical reaction of Falck, as well as some methods of impregnation made it possible to indentify enterochromaffin cells in the stomach of hyperthyroid rats and the rats after cortisone injection under the conditions ox hyperfunction of the thyroid gland. After 20 days of L-thyroxin injection, and after 10 days of hydrocortisone injection, preceded by L-thyroxin, the amount of enterochromaffin cells in the epithelial layer of the gastric mucosa were noted to increase that was accompanied by simultaneous increase of the number of secretory argyrophil granules in their cytoplasm. Simultaneous injection of L-thyroxin and hydrocortisone, while not decreasing statistically significant amount of the cells, produced degradation of their cytoplasm.     

Morphofunctional changes in the exocrine pancreatic cells in acute experimental pancreatitis in rats

Experimental pancreatitis was induced by cooling the splenetic part of rat pancreas with chlorethyl, and the cells of duodenal area of the pancreas were studied at different stages of pancreatitis using cytomorphometry, cytomorphology and autoradiography. Interlobular and interacinar oedemas were observed at the first hours after treatment. In 24 hours the intracellular oedema of exocrine pancreatic cells (EP) was detected. On day 14 after treatment typical acute edematous pancreatitis developed. The observed changes involve a pathological activation of EP of the duodenal area, a subsequent restoration of the structure of this area, and later a passage of pancreatitis into the chronic form. The usefulness of this model of pancreatitis for quantitative cytochemical studies of EP during pathogenesis and drug treatment is discussed.     

Morphofunctional changes in human flatfoot

The process of the flatfoot formation is accompanied not only by stretching but also by pressing of the plantar ligaments and muscles. In the plantar aponeurosis and ligaments subjected to pressing, adaptive rearrangements are observed; they are accompanied by transformation of the fibrillar connective tissue into cartilaginous one, that rather prevents the ligaments to affect the heigh of the fornix. In the structure of the plantar muscles rather noticeable changes occur, destructive ones including, that is seen in their microscopical picture.     

Morphofunctional changes in the chief cells of the intrinsic glands of the stomach in the presence of an excess of glucocorticoid and sex hormones in the body

In 260 male white rats electron microscopically, cytochemically with biochemical estimation of proteolitic activity of gastric juice, it has been demonstrated that principle cells of the gastric glands, after injection of small doses of hydrocorticone, respond with a complex of adequate ultrastructural, cytochemical and functional changes directed to realization of the drugs stimulating effect. With increasing time of the experiment, or the doses, progressively developing distrophic processes, involving predominantly the protein-synthesizing apparatus and, to a less degree, the mitochondrial mechanism, are observed in the principle cells. This results in inhibition of the pepsinogene synthesis phase and in decreasing proteolytic activity of gastric juice. Reaction of the principle cells is independent on testosterone doses; the protein-synthesizing and mitochondrial (to a less degree) apparatuses develop; the pepsinogene extrusion phase is suppressed; it results in its deposition in cytoplasm and in decreasing proteolytic activity of gastric juice. When testosterone and hydrocortisone are injected simultaneously in small doses, the stimulating effect of hydrocortisone to the principle cells is abolished and at large doses it is sharply manifested and is not accompanied with destructive changes in the principle cells.     

Morphofunctional changes in the endocrine system of the small intestine after its proximal resection

The influence of 50% proximal resection of the small intestine on the intestinal endocrine system was investigated on white male rats. The quantitative changes of argyrophil and argentaffin cells correlated with their secretory activity changes. The opposite character of secretory function synchronization was revealed on the 7th and 30th days along the length of the small intestine (proximo-distal sinusoid phenomenon). The secretory function normalization of the endocrine system is carried out in the distal and proximal direction along the length of the small intestine.     

Ultrastructural changes in the parietal cells of persons suffering gastric ulcers

Ultrastructural changes taking place in various phases of secretion in the gastric fundus parietal cells after histamine adminstration were studied in patients suffering from gastric and duodenal ulcers, having different gastric acidity. Parietal cells of patients with normal and hyperacidity of the gastric juice after histamine administration were found to have such ultrastructural alterations in which were characteristic of the intensively functioning cells, with the retention of phasic character of the process; as to patients with hypoacidity, the secretory phases of the parietal cells were not marked, and no alterations indicating intensification of the cellular functional activity were noted.     

Cadmium-induced changes in epithelial cells of the rat stomach

The aim of this study was to determine the changes in the function and fine structure of the gastric mucosa following exposure to high cadmium (Cd) for 30 d in rats. In the present study, control antimals were fed with normal food and tap water and the remaining animals received Cd (15 ppm CdCl₂) in drinking water for the same period. Receiving Cd for 30 d increased the mean blood (p<0.01) and mucosa (p<0.001) Cd levels, while decreased mucus thickness, mucin content (p<0.01) significantly. Basal acid output fell significantly (p<0.01). Light and electron microscopic examination revealed the following: (1) Cd decreases the mean number of surface mucous, isthmic-neck, parietal cells (p<0.05) and chief cells (p<0.001) per unit from the control value and (2) in some cells of zymogenic unit, the Cd-induced alterations were characterized with dilated Golgi cisternae, focal enlarged endoplasmic reticulum, broken tubulovesicles, degenerated mitochondria, dense nuclei, as well as lysosomal structures. We concluded that Cd augments the elimination rate of zymogenic unit’s cells by increasing the alteration rate, and the reduced basal acid output, mucin content, and mucus thickness can be explained easily with the loss of zymogenic unit’s cell population.     

Agonist-induced cytoplasmic volume changes in cultured rabbit parietal cells

Concomitant Na(+)/H(+) and Cl(-)/HCO(3)(-) exchange activation occurs during stimulation of acid secretion in cultured rabbit parietal cells, possibly related to a necessity for volume regulation during the secretory process. We investigated whether cytoplasmic volume changes occur during secretagogue stimulation of cultured rabbit parietal cells. Cells were loaded with the fluorescent dye calcein, and the calcein concentration within a defined cytoplasmic volume was recorded by confocal microscopy. Forskolin at 10(-5) M, carbachol at 10(-4) M, and hyperosmolarity (400 mosmol) resulted in a rapid increase in the cytoplasmic dye concentration by 21 +/- 6, 9 +/- 4, and 23 +/- 5%, respectively, indicative of cell shrinkage, followed by recovery to baseline within several minutes, indicative of regulatory volume increase (RVI). Depolarization by 5 mM barium resulted in a decrease of the cytoplasmic dye concentration by 10 +/- 2%, indicative of cell swelling, with recovery within 15 min, and completely prevented forskolin- or carbachol-induced cytoplasmic shrinkage. Na(+)/H(+) exchange inhibitors slightly reduced the initial cell shrinkage and significantly slowed the RVI, whereas 100 microM bumetanide had no significant effect on either parameter. We conclude that acid secretagoguges induce a rapid loss of parietal cell cytoplasmic volume, followed by RVI, which is predominantly mediated by Na(+)/H(+) and Cl(-)/HCO(3)(-) exchange.     

Morphofunctional changes of elements of a neurovascular bundle after torsion injury

In experiments performed on 32 animals using modern functional physiological and morphological techniques, certain changes in the vascular-nervous bundle elements have been studied at various degree of its distortion. The most pronounced changes at a similar degree of distortion occur in veins and arteries. The nerve possesses greater elasticity and traumatized at application of an essential mechanical force.     

The ultrastructure of the parietal cells of the stomach and their functional activity]

Submicroscopic changes in the parietal cells of the fundus were compared with the data of spot-film intragastric pH-metry of the same mucosal areas in 18 patients treated at the hospital in the department of therapeutic food deprivation. There were seen no changes in the ultrastructure of the parietal cells after a brief (36-hour) fasting when the pH of the mucous membrane failed to differ from the normal. With increased duration of food deprivation there occurred a gradual alkalinization of the gastric secretion and the pH of the gastric wall shifted from 2.02 after a 3-day food deprivation to 4.8-5.0 after fasting for 20 to 30 days. In accordance, there was a change in the ultrastructure of the parietal cells consisting in flattening and subsequent disappearance of tubulovesicles, a reduction of the lumina of the intracellular channels and shortening of microvilli. The results of comparison of the submicroscopic changes with the data of pH-metry indicated that such submicroscopic shifts corresponded co depression of the functional activity of the parietal cells.     

Epidermal growth factor inhibits cytoskeleton-related changes in the surface of parietal cells

The effect of epidermal growth factor (EGF) on gastric acid secretion was correlated with the morphological changes of the apical pole of rat parietal cells studied by transmission electron microscopy. Gastric acid secretion was stimulated by histamine, carbachol, pentagastrin, and insulin-induced hypoglycemia, and estimated by continuous recording of pH variations of gastric luminal perfusate. EGF inhibits acid secretion in these conditions. The action of the hormone also results in the arrest or reversal of the changes in shape undergone by parietal cells as they go into secretion. In view of the evidence involving cytoskeletal elements in the generation of these structural alterations, our observations suggest that the action of EGF on gastric acid secretion may be a consequence of a general effect of this hormone on cytoskeletal function.