Gastric Oxyntic Cells Research Articles

Gastric heterotopia-like duodenal polyps containing Brunner glands with abundant paneth cells and oxyntic cells are frequently associated with advanced left-sided colorectal polyps

Duodenal polyps mimicking gastric heterotopia but with abundant Paneth cells and occasional oxyntic cells in deep Brunner glands are difficult to classify, and the clinical significance of identifying these lesions is currently unknown. We report herein clinicopathological features of six of these lesions that arose in four patients. There were equal numbers of male and female, with an average age of 67. The average size of the polyps was 4.3 mm. All four patients had concurrent colorectal adenomatous polyps including two patients with giant left-sided tubulovillous adenomas measuring 55 mm and 44 mm. One patient had two left-sided traditional serrated adenomas. More than 10 gastric fundic gland polyps were found in two patients and one had a gastric hyperplastic/hamartomatous polyp. None of the patients had a known gastrointestinal polyposis syndrome. Histologically, all six lesions were characterised by a mixture of both gastric foveolar-type and small intestinal-type surface epithelium with deep Brunner glands containing abundant Paneth cells and occasional gastric oxyntic cells. Duodenal polyps mimicking gastric heterotopia but with abundant Paneth cells and oxyntic cells in deep Brunner glands are frequently associated with advanced left-sided colorectal polyps. Identifying such lesions in the duodenum may warrant a colonoscopy to rule out concurrent significant colorectal lesions.

Regeneration profiling of human gastric glands: differences between fundic and antral surface mucous cells

Introduction: Maintenance of the surface integrity of mucous epithelia is vital for physiological functions of many organs such as the stomach. The human gastric mucosa can be divided into three different functional regions, i.e., the cardia, the corpus, and the antrum. Classically, the cellular constituents are defined as surface mucous cells (SMCs)/gastric pit cells, oxyntic cells, mucous neck and antral gland cells, zymogenic cells and endocrine cells. Here, a first expression profile of human gastric glands is presented using RT-PCR analysis after laser microdissection.

S1945a Identification of TFF2 Expressing Cells as Specific Progenitors of Murine Gastric Oxyntic Mucosal Cells

S1945a Identification of TFF2 Expressing Cells as Specific Progenitors of Murine Gastric Oxyntic Mucosal Cells

Establishment of anti-rat-Cu,Zn-superoxide dismutase monoclonal antibodies applied to a highly sensitive immunoassay and immunohistochemistry system.

The superoxide anion has been implicated in a wide range of diseases. The major protector against superoxide anion in the cell cytosol is Cu,Zn-superoxide dismutase (Cu,Zn-SOD). In this study, anti rat Cu,Zn-SOD was established in murine monoclonal antibodies for the first time. These antibodies were applied to both a highly sensitive EIA system in serum and immunohistochemical methods for detection in gastric mucosa tissues. The proposed EIA method had a high sensitivity within the assay range, 10-300 pg/mL, good percentage, 96.9 +/- 5.60%, and good reproducibility; within-day assay CV = 8.6-10.2%, between-day assay CV = 6.5-11.7%. Inmmunohistochemically, Cu,Zn-SOD localized in the esophagus epithelial cells, gastric oxyntic cells, surface of the gastric lumen side in the small intestine and colonic epithelial cells. The establishment of anti-rat CuZn-SOD monoclonal antibody allows both specific analysis of immunoquantitation in rat Cu,Zn-SOD and highly specific detection of Cu,Zn-SOD location by immunohistochemical methods.

The effect of gender on Helicobacter felis‐mediated gastritis, epithelial cell proliferation, and apoptosis in the mouse model

The murine Helicobacter felis model has been extensively used to investigate the importance of host factors in the development of chronic gastritis. The effect of gender in this murine model is unknown. Male and female C57BL/6J mice were infected with H felis for up to 1 year. At 4, 8, 19, 36, and 52 weeks post-infection, gastric histopathology, epithelial cell proliferation, and apoptosis were examined and compared with age- and gender-matched controls. In female mice, infection with H felis resulted in an earlier onset of chronic gastric inflammation, epithelial hyperplasia, and oxyntic cell loss than males. In females, there was a trend towards increased gastric pathology compared with males, with long-term-infected female mice having significantly greater (p < 0.05) chronic inflammation than male mice. The histopathological differences in male and female mice did not relate to the density of H felis infection. Female mice infected with H felis had significantly increased gastric epithelial cell proliferation in the cardia and corpus at both 8 and 52 weeks post-infection (p < 0.05). Epithelial cell apoptosis in the glandular mucosa of the corpus at 36 and 52 weeks post-infection was significantly increased (p < 0.05) in female mice compared with uninfected gender controls. In contrast, there was no significant increase in epithelial cell proliferation or apoptosis in any area of the stomach at any time point after H felis infection in male mice. These results demonstrate that there are gender differences in the gastric inflammatory and epithelial response to H felis in the murine model. The functional importance of gender should be considered in future murine studies on H felis- and H pylori-induced chronic gastritis.

Ammonia and gastric acid secretion: a key to understanding activity and regulation of the H+,K+-ATPase

Ammonia is a cytotoxic substance liberated during Helicobacter pylori infection that may be responsible, in part, for the significant reduction in gastric acid secretion in human patients. However, it is not clear how ammonia blocks acid secretion. Here, we investigate several potential pathways for ammonia blockade in gastric oxyntic cells.___TAGSTART___BR___TAGEND___ Methods: Stomachs from the bullfrog, Rana catesbeiana, were stripped and mounted in Ussing chambers. Four possible pathways of blockade were investigated: (1) blockade of basolateral K+-channel activity, (2) blockade of ion transport activity, (3) neutralization of secreted H+ or (4) ATP depletion.___TAGSTART___BR___TAGEND___ Results: Addition of nutrient 10 mM NH4Cl at pH 7.4, yielding 92.5 μM NH3 and 9.91 mM NH4+, abolished acid secretion within 30 min. Inhibition of acid secretion did not occur by blockade of basolateral K+-channel activity or ion transport activity, nor did NH4+ enter cells by substituting for Na+ or K+ on individual ion transporters. Furthermore, neutralization of the luminal solution by NH3 and/or ATP depletion cannot account for the total reduction in acid secretion. We demonstrate that NH4Cl acts specifically on stimulated tissues.___TAGSTART___BR___TAGEND___ Conclusions: We show that small concentrations of ammonia completely block gastric acid secretion. We propose that inhibition of acid secretion occurs by blockade of an apical K+-channel, specifically inwardly rectifying K+-channels. Our data suggest that apical K+-channel activity may be essential for the regulation of acid secretion and could be a new therapeutic target for acid inhibitory drugs.

Interaction of alpha- and beta-subunits in native H-K-ATPase and cultured cells transfected with H-K-ATPase beta-subunit.

The assembly of the beta-subunit of the gastric H-K-ATPase (HKbeta) with the alpha-subunit of the H-K-ATPase or the Na-K-ATPase (NaKalpha) was characterized with two anti-HKbeta monoclonal antibodies (MAbs). In fixed gastric oxyntic cells, in H-K-ATPase in vitro, and in Madin-Darby canine kidney (MDCK) cells transfected with HKbeta, MAb 2/2E6 was observed to bind to HKbeta only when interactions between alpha- and beta-subunits were disrupted by various denaturants. The epitope for MAb 2/2E6 was mapped to the tetrapeptide S(226)LHY(229) of the extracellular domain of HKbeta. The epitope for MAb 2G11 was mapped to the eight NH(2)-terminal amino acids of the cytoplasmic domain of HKbeta. In transfected MDCK cells, MAb 2G11 could immunoprecipitate HKbeta with alpha-subunits of the endogenous cell surface NaKalpha, as well as that from early in the biosynthetic pathway, whereas MAb 2/2E6 immunoprecipitated only a cohort of unassembled endoglycosidase H-sensitive HKbeta. In HKbeta-transfected LLC-PK(1) cells, significant immunofluorescent labeling of HKbeta at the cell surface could be detected without postfixation denaturation or in live cells, although a fraction of transfected HKbeta could also be coimmunoprecipitated with NaKalpha. Thus assembly of HKbeta with NaKalpha does not appear to be a stringent requirement for cell surface delivery of HKbeta in LLC-PK(1) cells but may be required in MDCK cells. In addition, endogenous posttranslational regulatory mechanisms to prevent hybrid alpha-beta heterodimer assembly appear to be compromised in transfected cultured renal epithelial cells. Finally, the extracellular epitope for assembly-sensitive MAb 2/2E6 may represent a region of HKbeta that is associated with alpha-beta interaction.

Parietal cell membrane trafficking. Focus on "Expression of rab11a N124I in gastric parietal cells inhibits stimulatory recruitment of the H+-K+-ATPase".

gastric juice is highly acidic, and pH values of <1 are possible. This intragastric environment is achieved by the secretion of a primary fluid of ∼140 mM HCl by the mammalian gastric parietal or oxyntic cell. HCl secretion is elaborated across the apical membrane of the stimulated parietal cell

An immunologically distinct beta-adaptin on tubulovesicles of gastric oxyntic cells.

Clathrin and the gamma-adaptin subunit of the AP-1 clathrin adaptor have been previously identified on H-K-ATPase-rich tubulovesicles from gastric acid secretory (oxyntic) cells [C. T. Okamoto, S. M. Karam, Y. Y. Jeng, J. G. Forte, and J. Goldenring. Am. J. Physiol. 274 (Cell Physiol. 43): C1017-C1029]. We further characterized this AP-1 adaptor from rabbit and hog tubulovesicles biochemically and immunologically. Clathrin coat proteins were stripped from purified tubulovesicular membranes and fractionated by hydroxyapatite chromatography. The AP-1 adaptor appears to elute at 200 mM sodium phosphate, based on the presence of proteins in this fraction that are immunoreactive with antibodies against three of the four subunits of this heterotetrameric complex: the gamma-, mu1-, and sigma1-adaptin subunits. Although the putative beta-adaptin subunit in this fraction is not immunoreactive with the anti-beta-adaptin monoclonal antibody (MAb), this beta-adaptin is immunoreactive with polyclonal antibodies (PAbs) directed against the peptide sequence Gly625-Asp-Leu-Leu-Gly-Asp-Leu-Leu-Asn-Leu-Asp-Leu-Gly-Pro-Pro- Val640 , a region conserved between beta1- and beta2-adaptins that is thought to be involved in the binding of clathrin heavy chain. Immunoprecipitation of the AP-1 adaptor complex from this fraction with anti-gamma-adaptin MAb 100/3 resulted in the coimmunoprecipitation of the beta-adaptin that did not react with the anti-beta-adaptin MAb but did react with the anti-beta-adaptin PAbs. In contrast, immunoprecipitation of the AP-1 adaptor complex from crude clathrin-coated vesicles from brain resulted in the coimmunoprecipitation of a beta-adaptin that was recognized by both the anti-beta-adaptin MAb and PAbs. These results suggest that the tubulovesicular AP-1 adaptor complex may be distinct from that found in the trans-Golgi network and may contain an immunologically distinct beta-adaptin. This immunologically distinct beta-adaptin may be diagnostic of apical tubulovesicular endosomes of epithelial cells.

Characteristics of sodium uptake across the basolateral membrane of oxyntic cells

To characterize further serosal Na uptake into gastric oxyntic cells under resting conditions, cellular element concentrations were determined in isolated frog (Rana temporaria) gastric mucosae using electron microprobe analysis. The epithelia were kept short circuited in Ussing-type chambers, and element analysis was performed on freeze-dried cryosections. After ouabain (10(-4) M), the [Na] in oxyntic cells increased within 30 to 60 minutes from approximately 25 to 100 mmol/kg wet wt, and [K] decreased similarly (from 100 to 25 mmol/kg wet wt). These changes occurred regardless of whether the basolateral incubation medium contained HCO3 or N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) as buffers. When, prior to the addition of ouabain, 10(-3) M amiloride was applied to the serosal side to inhibit the Na-H antiporter, the ouabain-induced increase in cellular [Na] was prevented completely in HEPES-, but not in HCO3-Ringer. The data are compatible with the notion that Na is taken up by a Na-H antiporter and a Na-HCO3 symporter. At least under these experimental conditions, these transporters seem to contribute substantially to basolateral Na uptake in oxyntic cells.

Identification of clathrin and clathrin adaptors on tubulovesicles of gastric acid secretory (oxyntic) cells.

gamma-Adaptin and clathrin heavy chain were identified on tubulovesicles of gastric oxyntic cells with the anti-gamma-adaptin monoclonal antibody (MAb) 100/3 and an anti-clathrin heavy chain MAb (MAb 23), respectively. In Western blots, crude gastric microsomes from rabbit and rat and density gradient-purified, H-K-ATPase-rich microsomes from these same species were immunoreactive for gamma-adaptin and clathrin. In immunofluorescent labeling of isolated rabbit gastric glands, anti-gamma-adaptin and anti-clathrin heavy chain immunoreactivity appeared to be concentrated in oxyntic cells. In primary cultures of rabbit oxyntic cells, the immunocytochemical distribution of gamma-adaptin immunoreactivity was similar to that of the tubulovesicular membrane marker in oxyntic cells, the H-K-ATPase. Further biochemical characterization of the tubulovesicular gamma-adaptin-containing complex suggested that it has a subunit composition that is typical of that for a clathrin adaptor: in addition to the gamma-adaptin subunit, it contains a beta-adaptin subunit and other subunits of apparent molecular masses of 50 kDa and 19 kDa. From solubilized gastric microsomes from rabbit, gamma-adaptin could be copurified with the major cargo protein of tubulovesicles, the H-K-ATPase. Thus this tubulovesicular coat may bind directly to the H-K-ATPase and may thereby mediate the regulated trafficking of the H-K-ATPase at the apical membrane of the oxyntic cell during the gastric acid secretory cycle. Given the similarities of the regulated trafficking of the H-K-ATPase with recycling of cargo through the apical recycling endosome of many epithelial cells, we propose that tubulovesicular clathrin and adaptors may regulate some part of an apical recycling pathway in other epithelial cells.

Effect of pH buffers on proton secretion from gastric oxyntic cells measured with vibrating ion-selective microelectrodes.

Effect of pH buffers on proton secretion from gastric oxyntic cells measured with vibrating ion-selective microelectrodes.

Reflections on the analytical pharmacology of histamine H2-receptor antagonists

I n this essay I want to follow a train of thought that has occupied me, on and off, over the last 25 years. Generally, the essay is about trying to develop bioassays into instruments for pharmacological analysis. Specifically, I want first to rerun the discovery and classification of histamine Hz-receptor antagonists and then to see how much that classification has been useful in analyzing the physiological control of gastric oxyncic cell secretion. Bioassays based on intact tissues in vitro have some advantages over other types of assays. Thus, interactions between receptors expressed on the same cells can be studied directly, unlike studies based on radioligand binding in tissue homogenates or those using cloned receptors expressed on naive cells. Moreover, interactions between different cells in a tissue, organized in physiological format, can be studied in a way not possible with assays based on cell suspensions or tissue culture. However, these advantages of retained complexity are offset by the impenetrable “black box” lying between the initial pharmacological interaction with the tissue and the final physiological change in the state of the tissue. In spite of this, pharmacologists have two tactics open to them. First, they can simplify their systems by using native ligands to light up specific classes of proteins, enzymes, receptors, transporters, and so forth. Then they can use thought experiments to work out their expectations for outcomes of intera.ctions between native and foreign ligands and these specific molecular systems, according to assumed chemical rules. In this way, they design pharmacological models that relate hypothetical chemical interactions to measured physiological effects. The models then specify appropriate experimental designs to try to evaluate the model. Invariably, these designs call for the measurement of complete concentration-effect (or dose-response) relations. Usually these curves are symmetrical sigmoids in semilogarithmic space and can be uniquely characterized by three parameters; the potency (or dose for half-maximal effect), the amplitude (or maximum), and the slope (or sensitivity). These parameters are capable of independent variation and reflect significant changes of state in the system. Our models reflect these changes. In recent years, my group has designed a small library of explanatory models. My group, from the point of view of this essay, has included James Angus, Paul Leff, Nigel Shankley, and Nicola Welsh. My interest in histamine and gastric secretion started about 40 years ago. Following the discovery that 5-hydroxytryptamine (5-HT) was found in high concentration in the gastric mucosa, Adam Smith and I studied its effects on gastric secretion. We found that 5-HT produced an increase in mucus secretion and an inhibition of histamine-stimulated acid secretion.’ We explored this phenomenon for a while but mainly from the point of view of its physiological implications. However, long after the project ended I was still imprinted with an enthusiasm for the physiology and pharmacology of gastric oxyntic cell secretion. At that time, the well-known failure of the antihistamine drugs to block histamine-stimulated acid secretion had no message for me. However, the discovery of adrenaline P-receptor antagonists changed all that. The parallels between the pharmacology of histamine and adrenaline turned out to be quite striking.’ Antagonists to both of these agents, the antiadrenalines and antihistamines, were being discovered and characterized from the middle thirties onwards. These two classes of drugs shared some features. As a class, the antiadrenaline drugs were not obvious analogues of adrenaline nor were they structurally related to each

New fluorescent probes E3810 and methoxy E3810 for determining distributions of the apical membrane and the acidic compartment of gastric acid secreting cells.

Substituted benzimidazoles such as omeprazole, E3810 and methoxy E3810 were inhibitors of gastric H+, K(+)-ATPase which is rich in the apical membrane of gastric parietal or oxyntic cells at the secreting state. The acid-activated compounds of omeprazole and methoxy E3810, which have methoxy group at the 5-position in the benzimidazole ring, are fluorescent (excitation wavelength = 370 nm; emission wavelength = 560 nm). The fluorescence disappeared when the activated compounds reacted with the ATPase or glutathione. Using this fluorescence property, the distribution of the intracellular acidic canalicular space in isolated single parietal cells was determined. On the other hand, irradiation with ultraviolet light (335 nm) of the acid-activated compound of E3810 which had been reacted with sulfhydryl group of the ATPase or glutathione resulted in a formation of a fluorescent compound (emission = 470 nm). Using this second fluorescence property, we determined the distribution of the apical membrane of the intracellular canaliculus of isolated single mammalian parietal cells and also the location of the apical membrane on the external surface of newt oxyntic cells.

Selective internalization of the apical plasma membrane and rapid redistribution of lysosomal enzymes and mannose 6-phosphate receptors during osteoclast inactivation by calcitonin

The effects of inhibition of bone resorption by the peptide hormone calcitonin have been studied at the level of the osteoclast. Although not epithelial, the osteoclast is polarized with the secretion of newly synthesized lysosomal enzymes and of acid occurring specifically at the apical pole, facing the bone compartment. The membranes composing the apical (ruffled-border) and basolateral domains contain topologically restricted antigens, a 100 x 10(3) Mr lysosomal membrane protein and the Na+,K(+)-ATPase, respectively. It was found that calcitonin induces a rapid (15-60 min) redistribution of the apical marker as well as of markers of the secretory compartment of the osteoclast (arylsulfatase and cation-independent mannose 6-phosphate (Man6P) receptors). The apical plasma membrane, in contrast to the basolateral membrane, is selectively internalized. This internalization leads to the disappearance of the ruffled border. The vesicular translocation of apical membranes is reminiscent of the events occurring in gastric oxyntic cells and in kidney tubule intercalated cells during the regulation of acid secretion. In parallel, the synthesis of both the lysosomal enzyme arylsulfatase and Man6P receptors is arrested. The products that were already present in the secretory pathway seem to be rerouted to intracellular vacuoles instead of being targeted to the plasma membrane, leading to marked accumulation of enzymes in the inhibited cells. These results suggest that the rapid inhibition of bone resorption by calcitonin involves the vesicular translocation of the apical membranes and the rapid arrest in the synthesis and secretion of lysosomal enzymes in osteoclasts.

Detailed investigation of the diagnostic value in tumour histopathology of ICR.2, a new monoclonal antibody to epithelial membrane antigen

The production and detailed immunostaining properties of a new rat monoclonal antibody (ICR.2) to epithelial membrane antigen are reported. The antibody was selected for its ability to compete with the polyclonal antiserum (M7), used in the original immunohistological studies, in order that it might serve as a direct replacement in diagnosing epithelial tumours. Most of the staining reactions on normal tissues were identical to those previously reported with M7 but there were some important differences. They included: positivity of renal and adrenal capsular fibroblasts, perineurium, some myoepithelial and smooth muscle cells, occasional osteoblasts and squamous and thyroid follicular epithelium in the normal state. The intercellular canaliculi of sweat glands and secretory canaliculi of gastric oxyntic cells were clearly demonstrated. These staining reactions could be obtained with M7 when a sensitive detection system was used although the results were usually weak and inconsistent. Nearly all adenosquamous and transitional carcinomas were positive. The remaining tumours fell into three major groups: (1) those which were consistently or nearly consistently negative--melanoma, seminoma, rhabdomyosarcoma, alveolar soft part sarcoma, adrenal cortical carcinoma, granulocytic sarcoma, paraganglioma, non-Hodgkin's lymphoma. Hodgkin's disease and embryonal carcinoma: (2) those which were either negative or positive with distinctive patterns of staining--basal cell carcinoma, embryonal tumours: and (3) non-epithelial tumours that were consistently positive--epithelioid sarcoma, synovial sarcoma, osteosarcoma, chordoma and myeloma--or positive in a significant minority of cases--leiomyosarcoma, malignant fibrous histiocytoma, clear cell sarcoma of tendon sheath, various neuroectodermal tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of a 185-kDa band 3-related polypeptide in oxyntic cells

Polyclonal antibodies to the purified mouse erythrocyte anion exchange protein (band 3) and to a conserved COOH-terminal peptide of mouse band 3 (alpha-Ct) recognized a single major 185-kDa polypeptide in immunoblots of a membrane fraction prepared from rabbit gastric glands. Competition studies revealed that the epitopes shared between the rabbit gastric 185-kDa antigen and the approximately 100-kDa mouse erythrocyte band 3 protein are restricted to the COOH-terminal domain of band 3, which is known to contain the catalytic site for anion exchange activity. Immunofluorescence microscopy was used to demonstrate that this band 3-related polypeptide is associated with the plasma membrane in a subpopulation of gastric gland cells composed exclusively of oxyntic cells, as judged by the coincidence of immunofluorescence with alpha-Ct and with a monoclonal antibody to the gastric H+-K+-ATPase. This alpha-Ct-reactive antigen was further localized to the cytoplasmic face of the basolateral membrane of oxyntic cells, which correlates well with the physiologically determined site of anion exchange activity. These data demonstrate the presence in gastric oxyntic cells of a novel member of the family of proteins related to the erythrocyte anion exchanger. The possibility that the 185-kDa polypeptide is an anion exchanger is discussed.

Activation of Apical Chloride Channels in the Gastric Oxyntic Cell

Oxyntic cells that retain distinct morphological polarity between apical and basolateral membranes were isolated from the gastric mucosa of the amphibian Necturus. Patch-clamp techniques were applied to these cells to identify apical membrane ion channels associated with hydrochloric acid secretion. A single class of voltage-dependent, inwardly rectifying chloride channels was observed in the apical membranes of both resting and stimulated (acid-secreting) oxyntic cells. Stimulation of the cells with dibutyryladenosine 3',5'-monophosphate and isobutylmethylxanthine increased channel open probability and simultaneously increased apical membrane surface area. This chloride channel is probably responsible for electrogenic chloride secretion by the gastric mucosa and may also participate in the fluid- and enzyme-secretory functions of the oxyntic cell, analogous to the chloride channels found in the apical membranes of other exocrine cells.

Acid activation of omeprazole in isolated gastric vesicles, oxyntic cells, and gastric glands

Omeprazole, a potent inhibitor of gastric hydrogen ion transporting, potassium-stimulated adenosine triphosphatase, was found to be transformed into an SH-reactive strong fluorescent molecule (excitation and emission wavelengths of 370 and 560 nm, respectively) in an acidic medium. The addition of glutathione- or protein-containing sulfhydryl groups such as pepsin to the medium decreased the fluorescence. Also, the increase in the pH of the medium decreased the fluorescence. The fluorescent molecule was identified to be an acid-activated planar cyclic sulfenamide derivative of Omeprazole. The transformation was studied in H+-preaccumulated hog gastric vesicles, which contain the hydrogen ion transporting, potassium-stimulated adenosine triphosphatase. The addition of omeprazole to the vesicle suspension induced a rapid increase in the fluorescence intensity, indicating that omeprazole was activated in the intravesicular space. Then, the intensity biphasically decreased with time. The slower small decrease was due to the reaction of the sulfenamide with sulfhydryl group(s) located on the acid secretory side of the hydrogen ion transporting, potassium-stimulated adenosine triphosphatase. Omeprazole was also activated in the acidic lumina of isolated rabbit gastric glands that were stimulated with histamine. Furthermore, direct evidence was obtained from the imaging of the fluorescence that omeprazole was activated in the acidic compartments of the isolated Xenopus oxyntic cell.

Polarity and Membrane Transport in Osteoclasts

The osteoclast is a highly polarized non-epithelial cell. The apical pole of the cell is determined by the cell's attachment to the extracellular matrix. This attachment forms the sealing zone, delimiting the subosteoclastic bone resorbing compartment. The apical membrane of the cell forms the ruffled-border, which contains some specific membrane proteins and a proton pump ATPase, which acidifies the apical compartment. Newly synthesized lysosomal enzymes are vectorially transported into this apical compartment bound to mannose-6-phosphate receptors. The basolateral membrane is highly enriched in sodium pumps with beta and alpha 1 subunits. Associated with the acidification process is the carbonic anhydrase found in the cytoplasm and membrane-associated and a bicarbonate-chloride exchanger in the membrane.2 These features put the osteoclast in the same functional category as the kidney tubule intercalated cell and the gastric oxyntic cell, both of epithelial origin, which secrete acid in a polarized fashion.