Parietal Cell Function Research Articles

Selective inhibition by somatostatin of cyclic AMP production in rat gastric glands: Demonstration of a direct effect on the parietal cell function

Somatostatin, originally isolated from the hypothalamus as an inhibitor of growth hormone secretion [I], is released from somatostatin~ontaining D cells of the stomach [2] and pancreas [2,3] during the gastric phase of a meal [4]. In vivo, somatostatin is reported to inhibit the pepsinogen secretion induced by a meal [S] and the gastric acid secretion stimulated by histamine [6,7]. The presence of specific receptors for somatostatin on isolated gastric cells from the rat fundus [8] strongly suggests that somatostatin exerts a direct effect on these exocrine secretory processes: We have shown that secretin which stimulates pepsinogen [9] and mucous [lo] secretions is highly potent in stimulating cyclic AMP production in gastric glands isolated from the rat fundus and antrum, while histamine is only effective on the acid-secreting fundic preparation [ 1 l]. Here we have examined therefore the ability of somatostat~ to inhibit both secretin and histamine-induced cyclic AMP formation in our system. The effect of cimetidine, a specific Hz-receptor antagonist [ 121 was also investigated since it has been shown that histamine stimulates gastric acid secretion by interacting with an Hz-receptor cyclic AMP system [ 131 present in parietal cells ]14]. Our data demonstrate that somatostatin (1 O-‘low6 M) reduces considerably the effect of histamine on the cyclic AMP production in a non-competitive way, while cimetidine (1 O-*-l O4 M) inhibits competitively the histamine stimulation. In contrast, no effect of somatostatin was found on the cyclic AMP

Endocrinology of duodenal ulcer.

Several gastrointestinal peptides with proven or suggested endocrine or paracrine functions influence gastric acid secretion, gastrointestinal motility, and mucosal blood flow. Increased or decreased release of such factors could participate in the pathogenesis of duodenal ulcer disease by inducing increased gastric acid concentration in the duodenal bulb. To date, increased stimulation of parietal cells by gastrin has been demonstrated only in patients with gastrinoma, G-cell hyperplasia, gastric outlet obstruction, hyperparathyroidism, excluded antrum, and short bowel syndrome, but not in the usual duodenal ulcer disease. Also, a defective inhibition of parietal cell function by endocrine or paracrine factors, such as gastric inhibitory polypeptide, secretin, somatostatin and vasoactive intestinal polypeptide, seems not to exist in patients with duodenal ulcer disease. However, as long as the physiology of gastrointestinal peptides in gastric secretion and motility is not understood, a possible role of these factors in the pathogenesis of simple duodenal ulcer disease cannot be excluded.

Hormonal control of parietal cell function.

AbstractIn order to study the actions of secretagogues and inhibitors of acid secretion, parietal cells have been isolated from canine fundic mucosa. Prepared by the sequential exposure to collagenase and EDTA of mucosa that has been bluntly separated from submucosa, these parietal cells retain responsiveness to stimulation as evidenced by increases in oxygen uptake and aminopyrine accumulation, and by undergoing the morphologic transformation that characterizes the stimulated parietal cell in intact mucosa. Cimetidine and atropine specifically inhibited the effects of histamine and carbachol, respectively, but failed to inhibit the small response to gastrin, which indicates that the parietal cell has separate and specific receptors for each of these two stimulants plus a third receptor for gastrin. Furthermore, potentiating interactions were found between histamine and gastrin, and histamine and carbachol, but not between carbachol and gastrin. However, when parietal cells were treated simultaneously with histamine, gastrin, and carbachol, in concentrations that when acting alone produced threshold stimulation, a three‐way potentiating interaction was found. In the presence of these combinations, atropine and cimetidine retained their respective specificities against carbachol and histamine. The specific actions of these inhibitors may explain their apparent nonspecificity in vivo in that, by blocking the histamine and carbachol components of potentiating interactions, the agents will appear to block the actions of the pharmacologically unrelated components of the interaction. Thus, in vivo, if the parietal cell were under sufficient effects from endogenous histamine and acetylcholine to support potentiating interactions, then the potentiated response to superimposed stimuli such as gastrin would be inhibited by both cimetidine and atropine.

Uremic Gastropathy in the Dog

Stomachs of four dogs with uremia and four normal dogs were examined. Uremic stomachs represented four types of disease: atrophic, amyloidotic, ulcerative and necrotic gastropathy. Pathologic changes common to all uremic stomachs were expansion of the lamina propria, atrophy of gastric glands, and submucosal arteriopathy; lesions were limited to body and fundic zones. Lamina propria was markedly expanded by edema, mastocytosis, deposition of acidic mucosubstances, fibroplasia and mineralization. Capillaries in lamina propria had swollen endothelium and calcium salts were present extracellularly as amorphous granular laminae. Gastric glands were distorted and irregular and had fewer cells per unit of tissue. Parietal cells were swollen and had fragmentation of cytocavitary network and mitochondrial swelling with calcification. Chief cells were shrunken, agranular and atrophic with foci of glycogen and dilation of endoplasmic reticulum. Argentaffin cell content was diminished. Muscular arteries of submucosae had segmental degenerative lesions characterized by myocyte necrosis, calcification, and deposition of acidic mucosubstances and fibrin; thrombosis and obstructive arteriopathy were common. These studies suggest that uremic gastropathy is a disease of mucosal lamina propria and that lesions were due to anoxia caused by diffuse vascular injury and to altered parietal cell function.

Interaction of Calcium, Magnesium, and Gastrin on Gastric Acid Secretion

A dose response study of the effect on gastric acid secretion of synthetic human gastrin-17 (SHG) in doses of 50, 200, and 500 ng/kg/hr was performed in 8 healthy volunteers. The study was repeated on separate days during i.v. infusion of magnesium sulphate (0.4 meq Mg2+/kg/hr), of calcium gluconate (0.1 meq Ca2+/kg/hr) and of magnesium sulphate plus calcium gluconate. Magnesium infusion resulted in an increase in the dose of SHG required for one-half maximal secretion (D50), whereas infusion of calcium decreased D50. The difference in D50 of SHG when administered in combination with magnesium and with calcium was significant. Combined infusion of SHG, magnesium, and calcium resulted in the same D50 of SHG as found when SHG was infused alone. The calculated maximal acid response was almost identical in the four experiments except for a minor but nonsignificant decrease during calcium infusion. The results indicate an interaction of calcium, magnesium, and gastrin on parietal cell function and extend the observations of others in intact humans as well as in isolated gastric mucosa.

Effect of long-term gastrin stimulation on structure and function of rat parietal cells

Effect of long-term gastrin stimulation on structure and function of rat parietal cells

Effect of p-Chloromercuribenzene Sulfonate on Gastric Parietal and Surface Cell Function in the Dog

p-Chloromercuribenzene sulfonate, a polar organic mercurial which presumably penetrates cell membranes with great difficulty, led to a profound decrease in acid recovered from exteriorized segments of dog gastric fundus stimulated by exogenous histamine. Trapping of secreted hydrogen ions by Tris buffer did not significantly reduce the back-diffusion component of apparent inhibition. Sodium-for-hydrogen exchange was close to unity before and after inhibition.

Influences of hemigastrectomy and vagotomy on the function of parietal cells of the stomach

Influences of hemigastrectomy and vagotomy on the function of parietal cells of the stomach

Effect of stimulators and inhibitors of hydrochloric acid secretion on numbers of oxidoreductase-positive gastric parietal cells in rats

Frequency counts of gastric parietal cells with positive reactions for six oxidoreductases were performed in 30 rats treated with stimulators and inhibitors of hydrochloric acid secretion. Insulin and reserpine selectively increase the number of cells with positive histochemical reactions for the enzymes involved in anaerobic glycolysis, the Krebs cycle and the respiratory chain, and enhance their predominance observed under basal conditions. Probantine, secretin and depepsen, on the other hand, diminish the number of the same oxidoreductase-positive cells, thus reducing the differences between them and the enzymes belonging to other biochemical pathways (pentose phosphoric shunt, amino acid and ketone bodies metabolism). It seems probable that the stimulators, as well as the inhibitors, influence selectively those enzymes whose activity offers a metabolic basis for the characteristic function of the gastric parietal cells, namely hydrochloric acid secretion.

Effect of partial dehydration of ex vivo canine stomach on secretory function.

Isolated whole canine stomachs were dehydrated for 4 h and then perfused <i>ex vivo </i>with homologous blood of living supporting dogs. Dehydration was produced by vacuum during which temperatures fell to –3 °C. During the perfusion period, stomachs were stimulated intra-arterially with histamine and a cholinergic drug. Blood and gastric juice (30-min samples) were studied for various components. Perfusion lasted from 6 to 8 h. The secretory function of seven dehydrated-perfused stomachs was compared with that of seven stomachs perfused without prior preservation. Dehydration resulted in loss of about one third of the gastric tissue water. When the dehydrated, hypothermic stomach was connected with normothermic homologous perfusion blood, in 30 min it regained its motility and after a 30- to 90-min ‘rest’ started to secrete titratable H⁺ and pepsin. In 5–8 h of perfusion, all previously dehydrated stomachs regained their water content. The perfusion method described in this study represents a model for assessing the functional viability of an organ preserved prior to transplantation. Viability and function of parietal and chief cells of the gastric mucosa was not lost, despite prolonged anoxia and marked dehydration of the whole canine stomach, as demonstrated by <i>ex vivo</i> perfusion.

Selective vagotomy of the gastric remnant for extragastric ulcer recurrence following resection.

Ulcers may be the resultant of overstressed physiological tissue function, in the antrum stimulated by stasis or reduced parietal cell function, in the duodenum when the inhibitory mechanisms are overactivated by increased parietal cell function. Primary and secondary antral ulcers are treated by antrectomy, duodenal ulcers and extragastric recurrent ulcers by selective gastric vagotomy. One of 20 patients died after selective vagotomy of the gastric remnant for extragastric recurrence. Postoperative spontaneous secretions were alkaline in all cases, and 18 of 19 patients were achlorhydric on insulin activation. Pentapeptide-activated secretion was abolished in half the patients and otherwise reduced by 80 per cent.

Differential effects of--SH reagents on transport and electrical properties of gastric mucosa.

ARTICLESDifferential effects of--SH reagents on transport and electrical properties of gastric mucosa Solberg LA Jr, and JG Forte Solberg LA Jr, and JG FortePublished Online:01 May 1971https://doi.org/10.1152/ajplegacy.1971.220.5.1404MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited BySulphydryl modification inhibits taurine transport in human placental brush border membranesPlacenta, Vol. 17, No. 5-6p-Chloromercuribenzoate Causes Ca 2+ -Dependent Exocytotic Catecholamine Secretion from Cultured Bovine Adrenal Medullary CellsJournal of Neurochemistry, Vol. 53, No. 1Mechanism of gastric antisecretory effects of nolinium bromideGastroenterology, Vol. 85, No. 4Secretagogue-induced transport of H+ and K+ by in vitro amphibian gastric mucosaBiochemical Pharmacology, Vol. 29, No. 20Gastric SecretionAltered Permeability of Cell Membranes1 January 2011Effect of p-Chloromercuribenzene Sulfonate on Gastric Parietal and Surface Cell Function in the DogGastroenterology, Vol. 68, No. 2Ion Transport and Short-Circuit TechniqueSecretory Events in Gastric MucosaGlycoproteins and glycolipids of oxyntic cell microsomes I. Glycoproteins: Carbohydrate composition, analytical and preparative fractionationBiochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 307, No. 2Conductance of epithelial tissues with particular reference to the frog's cornea and gastric mucosaExperimental Eye Research, Vol. 15, No. 5 More from this issue > Volume 220Issue 5May 1971Pages 1404-1412 Copyright & PermissionsCopyright © 1971 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1971.220.5.1404PubMed5574658History Published online 1 May 1971 Published in print 1 May 1971 Metrics

Effect of vagotomy and-or antrectomy on gastric secretion stimulated by intravenous infusion of bethanechol chloride. Study on rats with gastric fistula.

The interdigestive phase of gastric secretion was investigated for 24 hr in rats bearing permanent gastric fistulas. Intact controls, vagotomized, antrectomized and vagotomized-antrectomized animals were studied. Vagotomy, alone or combined with antrectomy, abolished the secretory function of parietal and zymogenic cells during the spontaneous interdigestive phase of secretion. This was considered due to the fact that the interdigestive secretion is vagus dependent and represents a true cephalic phase. Antrectomy did not result in the decrease of spontaneous secretion of HCl or pepsin. Intra-arterial stimulation with a stable choline ester, bethanechol, produced adequate secretory response in intact rats and partially restored the function of parietal cells in vagotomized rats. The action of bethanechol on HCl secretion in antrectomized rats was less marked. However, bethanechol has a very marked stimulatory effect on the secretion of pepsin in intact, vagotomized and antrectomized rats. Sensitivity of gastric mucosa to bethanechol was nearly abolished in vagotomized-antrectomized rats.

Effect of 2-deoxy-D-glucose on gastric secretion in rats.

Stimulation of gastric secretion was produced in gastric fistula bearing rats infused i.v. for 24 h with 2-deoxy D-glucose (2-DG). When 2-DG was infused simultaneously with maximal dose of histamine, gastric secretion was higher than when stimulated with either of these stimulants given separately Bilateral vagotomy abolished the secretory function of Vagotomy parietal and zymogenic cells during the non-stimulated, interdigestive phase of gastric secretion in rats. Bilateral vagotomy abolished also 2-DG stimulated gastric secretion and significantly decreased the post-histamine gastric secretion. It appears that 2-DG acts on gastric mucosa only in the presence of intact vagi. The presence of vagi also enhances the action of histamine on gastric secretion.

Absorption and malabsorption of vitamin B 12

Prerequisites for the active, physiologic absorption of vitamin B 12 are adequate intrinsic factor (IF) secretion (and therefore gastric parietal cell function), normal ileal mucosal receptor sites and optimal intraluminal conditions for the attachment of the IF-B 12 complex to its receptor site. Conditions that affect the structure and/or function of the gastric parietal cells and/or ileal receptor sites may therefore result in vitamin B 12 malabsorption. Similarly, clinical states in which the intraluminal ileal pH and ionic milieu are affected may result in malabsorption of vitamin B 12. Intraluminal agents such as bacteria or parasites, by competing with the host for dietary vitamin B 12, constitute another cause of vitamin B 12 deficiency.

Gastric hyposection produced in rats by long-term oral administration of glycopyrrolate.

An anticholinergic drug, 1-methyl-3-pyrrolidyl-2-phenylcyclopentaneglycolate methobromide (glycopyrrolate) dissolved in drinking water, was given to the rats. The treatment lasted for 5 months. A secretion study was then performed in gastric fistula-bearing animals, infused for 24 h with normal saline or histamine. A significant decrease of the secretory function of parietal and zymogenic cells was found in treated rats, as compared with untreated control animals. Long-term administration of an anticholinergic drug in drinking water appears to be an easy experimental method of induction of gastric secretory hypofunction in rats.

Ultrastructure and Function of Gastric Parietal Cells in the Rat During Development

Three different aspects of the development of the gastric mucosa were investigated in the rat, viz., pH of gastric contents after histamine stimulation, activity of carbonic anhydrase in stomach homogenates, and ultrastructure of the epithelial cells, particularly the developing parietal cells. Gastric pH decreased from 5.3 immediately after birth to about 2.7 in 10-day-old rats. Carbonic anhydrase activity was first demonstrated in rat embryos on the 20th day of gestation. Electron microscopy revealed that primitive parietal cells can be positively identified from the same age. These cells are characterized by intracellular canaliculi lined with microvilli, and the cytoplasm contains a fair number of mitochondria, numerous ribosomes, a moderately well developed rough surfaced endoplasmic reticulum, and a few dense granules. Practically all of these granules disappear before 10 days of age; at the same time, cytoplasmic vacuoles increase in number. Lysosome-like bodies are frequently found during the first 10 days after birth. A dense substance is often observed in the parietal cell canaliculi of the developing rats; this could be a carrier for hydrochloric acid.

Influence of dietary fat on histamine stimulated gastric secretion in rats.

Gastric secretory function was studied for 24 h in rats bearing permanent gastric fistulas and permanent intra-venous cannulas. Rats were fed normal, fat free and rich fat diets for three months prior to collection of gastric content. Saline or histamine in saline were infused intravenously for 24 h during the collection period. Feeding fat rich diet induced the significant depression of histamine stimulated gastric secretion.The absence of normal post-histaminic increase of gastric secretory function in ratsfed fat rich diet is considered due to “work hypoplasia”, resulting from prolongedand repeated inhibition of secretory function of parietal cells.

Comparative effect of long-term anticholinergic administration with glycopyrrolate and of vagotomy on parietal cell function, ultrastructure, and population.

1. Long-term oral administration of an anticholinergic, glycopyrrolate, induces a progressive inhibition of histamine-stimulated parietal cell secretion in dogs, provided the drug is given prior to histamine injection; no inhibition is evident without prehistamine glycopyrrolate. 2. Glycopyrrolate administration prior to histamine injection induces an additional inhibitory response in vagotomized dogs over and above that resulting from vagotomy alone. 3. Ultrastructural parietal cell morphologic changes develop in dogs following long-term administration of glycopyrrolate. 4. Parietal cell changes of a similar type develop in rats following long-term administration of glycopyrrolate. 5. No parietal cell derangements are found in dogs following vagotomy. 6. No changes in parietal cell population are found in dogs or rats following long-term administration of glycopyrrolate or in dogs subjected to vagotomy. 7. Long-term administration of glycopyrrolate is apparently more effective than vagotomy in inhibiting secretion.

Effect of calcium infusion on gastric function in rats.

Rats having permanent gastric fistulas were infused intravenously for 24 hours with calcium in saline, or with saline alone. Gastric secretion was collected for the period of infusion. In calcium-treated rats significant reduction of gastric acid secretion was found. In these animals blood pepsinogen was increased but gastric tissue pepsinogen was reduced. Reduction of zymogenic granules of chief cells was also found in glandular mucosa of calcium-infused rats. Hypercalcemia appeared to alter the function of both parietal and chief cells of rat stomach under the conditions of this experiment.