Vitamin B12 deficiency may play an etiological role in atrophic glossitis and its grading: A clinical case-control study.

BACKGROUND: Existing studies have reported the significant association between atrophic glossitis (AG) and hematinic deficiencies, including iron, folate and vitamin B12 deficiency. However, these findings were inconsistent. AG can be graded as partial or complete atrophy. It is still unclear whether hematinic deficiencies are associated with the grading of AG. METHODS: 236 AG patients and 208 sex- and age-matched healthy controls were enrolled in this study. Hematological tests including complete blood count, and serum levels of folate, ferritin and vitamin B12 were performed. The AG group was divided into those with partial AG and those with complete AG according to the extent of papillary atrophy. Statistical analysis was performed to assess whether hematinic deficiencies are risk factors for AG and its grading. RESULTS: Compared with the healthy controls, AG patients had significantly higher frequencies of vitamin B12 deficiency (68.22%), ferritin deficiency (13.98%) and anemia (21.61%). The differences in hematinic deficiencies and anemia between AG patients and healthy controls changed according to gender and age. The frequencies of serum vitamin B12 deficiency and anemia in the complete AG subgroup were significantly higher than those in the partial AG subgroup. Logistic regression analysis revealed that vitamin B12 deficiency and anemia were significantly correlated with AG and its grading. The AG patients with vitamin B12 deficiency responded well to supplement therapy. CONCLUSION: AG could be an important clinical indicator for potential vitamin B12 deficiency, especially when the degree of tongue atrophy more than 50% and complete atrophy. Vitamin B12 deficiency might play an etiological role in the development of AG.

The A2B adenosine receptor colocalizes with adenosine deaminase in resting parietal cells from gastric mucosa.

The A2B adenosine receptor (A2BR) mediates biological responses to extracellular adenosine in a wide variety of cell types. Adenosine deaminase (ADA) can degrade adenosine and bind extracellularly to adenosine receptors. Adenosine modulates chloride secretion in gastric glands and gastric mucosa parietal cells. A close functional link between surface A2BR and ADA has been found on cells of the immune system, but whether this occurs in the gastrointestinal tract is unknown. The goal of this study was to determine whether A2BR and ADA are coexpressed at the plasma membrane of the acid-secreting gastric mucosa parietal cells. We used isolated gastric parietal cells after purification by centrifugal elutriation. The membrane fraction was obtained by sucrose gradient centrifugation. A2BR mRNA expression was analyzed by RT-PCR. The surface expression of A2BR and ADA proteins was evaluated by Western blotting, flow cytometry and confocal microscopy. Our findings demonstrate that A2BR and ADA are expressed in cell membranes isolated from gastric parietal cells. They show a high degree of colocalization that is particularly evident in the surface of contact between parietal cells. The confocal microscopy data together with flow cytometry analysis suggest a tight association between A2BR and ADA that might be specifically linked to glandular secretory function.

The Golgi apparatus in the endomembrane-rich gastric parietal cells exist as functional stable mini-stacks dispersed throughout the cytoplasm.

BACKGROUND INFORMATION: Acid-secreting gastric parietal cells are polarized epithelial cells that harbour highly abundant and specialized, H+,K+ ATPase-containing, tubulovesicular membranes in the apical cytoplasm. The Golgi apparatus has been implicated in the biogenesis of the tubulovesicular membranes; however, an unanswered question is how a typical Golgi organization could regulate normal membrane transport within the membrane-dense cytoplasm of parietal cells. RESULTS: Here, we demonstrate that the Golgi apparatus of parietal cells is not the typical juxta-nuclear ribbon of stacks, but rather individual Golgi units are scattered throughout the cytoplasm. The Golgi membrane structures labelled with markers of both cis- and trans-Golgi membrane, indicating the presence of intact Golgi stacks. The parietal cell Golgi stacks were closely aligned with the microtubule network and were shown to participate in both anterograde and retrograde transport pathways. Dispersed Golgi stacks were also observed in parietal cells from H+,K+ ATPase-deficient mice that lack tubulovesicular membranes. CONCLUSIONS: These results indicate that the unusual organization of individual Golgi stacks dispersed throughout the cytoplasm of these terminally differentiated cells is likely to be a developmentally regulated event.

Effects of extracts of oxyntic mucosa in rat on the biological activity of osteoblasts.

UNLABELLED: We explored the relationship between extracts of oxyntic mucosa (EOM) and the biological activity of osteoblasts in rats. We found that EOM could enhance the activity of bone formation in osteoblast. Our results suggest that EOM likely play a role in the cases of osteopenia induced by gastrectomy. INTRODUCTION: Surgical removal of the stomach (gastrectomy) leads to osteopenia in animals and in humans. It was demonstrated that EOM could induce transient hypocalcaemia and stimulate an uptake of Ca(2+) into bone in rats. The main aim of this study has been to clarify whether this procedure was performed through osteoblast, which is responsible for bone formation. METHODS: Osteoblasts were isolated, cultured, and identified in vitro. Preparing the rats' EOM and diluting into low, middle, and high concentrations, respectively. After osteoblasts were treated by different concentration EOMs or saline (for control), the intracytoplasm [Ca(2+)]i was measured by laser scanning confocal microscopy; the proliferation of osteoblast cells were detected with cell counting kit 8 (CCK-8); and the expressions of collagen type I and osteocalcin were assayed by reverse transcriptase polymerase chain reaction and Western blot. RESULTS: EOMs were found to induce a dose-related rapid increase of intracytoplasm [Ca(2+)]i in osteoblasts and could stimulate osteoblasts to enhance proliferation and upregulate the expressions of collagen type I and osteocalcin significantly (p < 0.05) compared with the control group. CONCLUSIONS: It was confirmed that EOM could stimulate osteoblasts to elevate the cytoplasm [Ca(2+)]i and promote the multiplication and the activity of bone formation in osteoblasts.

An ion-transporting ATPase encodes multiple apical localization signals.

Epithelial cells accumulate distinct populations of membrane proteins at their two plasmalemmal domains. We have examined the molecular signals which specify the differential subcellular distributions of two closely related ion pumps. The Na,K-ATPase is normally restricted to the basolateral membranes of numerous epithelial cell types, whereas the H,K-ATPase is a component of the apical surfaces of the parietal cells of the gastric epithelium. We have expressed full length and chimeric H,K-ATPase/Na,K-ATPase cDNAs in polarized renal proximal tubular epithelial cells (LLC-PK1). We find that both the alpha and beta subunits of the H,K-ATPase encode independent signals that specify apical localization. Furthermore, the H,K-ATPase beta-subunit possesses a sequence which mediates its participation in the endocytic pathway. The interrelationship between epithelial sorting and endocytosis signals suggested by these studies supports the redefinition of apical and basolateral as functional, rather than simply topographic domains.

Polarized distribution of actin isoforms in gastric parietal cells.

The actin genes encode several structurally similar, but perhaps functionally different, protein isoforms that mediate contractile function in muscle cells and determine the morphology and motility in nonmuscle cells. To reveal the isoform profile in the gastric monomeric actin pool, we purified actin from the cytosol of gastric epithelial cells by DNase I affinity chromatography followed by two-dimensional gel electrophoresis. Actin isoforms were identified by Western blotting with a monoclonal antibody against all actin isoforms and two isoform-specific antibodies against cytoplasmic beta-actin and gamma-actin. Densitometry revealed a ratio for beta-actin/gamma-actin that equaled 0.73 +/- 0.09 in the cytosol. To assess the distribution of actin isoforms in gastric glandular cells in relation to ezrin, a putative membrane-cytoskeleton linker, we carried out double immunofluorescence using actin-isoform-specific antibodies and ezrin antibody. Immunostaining confirmed that ezrin resides mainly in canaliculi and apical plasma membrane of parietal cells. Staining for the beta-actin isoform was intense along the entire gland lumen and within the canaliculi of parietal cells, thus predominantly near the apical membrane of all gastric epithelial cells, although lower levels of beta-actin were also identified near the basolateral membrane. The gamma-actin isoform was distributed heavily near the basolateral membrane of parietal cells, with much less intense staining of parietal cell canaliculi and no staining of apical membranes. Within parietal cells, the cellular localization of beta-actin, but not gamma-actin, isoform superimposed onto that of ezrin. In a search for a possible selective interaction between actin isoforms and ezrin, we carried out immunoprecipitation experiments on gastric membrane extracts in which substantial amounts of actin were co-eluted with ezrin from an anti-ezrin affinity column. The ratio of beta-actin/gamma-actin in the immunoprecipitate (beta/gamma = 2.14 +/- 0.32) was significantly greater than that found in the cytosolic fraction. In summary, we have shown that beta- and gamma-actin isoforms are differentially distributed in gastric parietal cells. Furthermore, our data suggest a preferential, but not exclusive, interaction between beta-actin and ezrin in gastric parietal cells. Finally, our results suggest that the beta- and gamma-actin-based cytoskeleton networks might function separately in response to the stimulation of acid secretion.

Characterization by Lectin Histochemistry of Two Subpopulations of Parietal Cells in the Rat Gastric Glands.

Parietal cells undergo a differentiation process while they move from the isthmus toward the pits and the base region of the gastric gland. The aim of this work was to analyze the rat gastric glands by lectin histochemistry to show the glycans expressed by upper (young) and lower (old) parietal cells. We used lectins recognizing the most frequent sugar moieties in mammals. Each lectin was assayed alone and in combination with several deglycosylation pretreatments: (1) ß-elimination, which removes O-linked oligosaccharides; (2) incubation with Peptide-N-glycosidase F, to remove N-linked glycans; (3) acid hydrolysis, which removes terminal sialic acid moieties; (4) methylation-saponification, to remove sulfate groups from sugar residues; and (5) glucose oxidase, a technique carried out with the lectin concanavalin A to convert glucose into gluconic acid. The lectins from Helix pomatia, Dolichos biflorus (DBA), Glycine max (soybean), Maclura pomifera, Arachis hypogaea (peanut), Bandeiraea simplicifolia (lectin I-B4), and Datura stramonium showed a different glycan expression in the parietal cells throughout the gastric gland. This difference supports that parietal cells undergo a maturation/degeneration process while the cells descend along the gland. The role of DBA as a marker of parietal cells previously reported should be taken with caution because these cells showed different reactivity for the lectin, ranging from negative to strong labeling.

Immunocytochemical identification of low-affinity NTS2 neurotensin receptors in parietal cells of human gastric mucosa.

The biological effects of neurotensin (NT) are mediated by two distinct G protein-coupled receptors, NTS(1) and NTS(2). Although it is well established that neurotensin inhibits gastric acid secretion in man, the plasma membrane receptor mediating these effects has not been visualized yet. We developed and characterized a novel antipeptide antibody to the carboxy-terminal region of the human NTS(2) receptor. The cellular and subcellular distribution of NTS(2) receptors was evaluated in various human gastrointestinal tissues. Specificity of the antiserum was demonstrated by (1) detection of a broadband migrating at M(r) 90 000-100 000 in Western blots of membranes from NTS(2)-expressing tissues; (2) cell-surface staining of NTS(2)-transfected cells; (3) translocation of NTS(2) receptor immunostaining after agonist exposure; and (4) abolition of tissue immunostaining by preadsorbtion of the antibody with its immunizing peptide. In the gastrointestinal tract, NTS(2) receptor immunoreactivity was highly abundant in parietal cells of the gastric mucosa, in neuroendocrine cells of the stomach small and large intestine, and in cells of the exocrine pancreas. NTS(2) receptors were clearly located in the plasma membrane and uniformly present on nearly all target cells. The presence of NTS(2) receptors was rarely detected in human tumors. This is the first localization of NTS(2) receptors in human formalin-fixed, paraffin-embedded tissues at the cellular level. The abundant expression of low-affinity NTS(2) receptors on the plasma membrane of human parietal cells provides a morphological substrate for the direct inhibition of gastric acid secretion observed after i.v. administration of neurotensin.

[A pH-probe for endoscopic parietal topographical pH-metry].

A pH-probe for endoscopic parietal topographical pH-metry was developed. The probe has a circular measuring electrode and a cutaneous silver chloride reference electrode. Clinical testing of the developed probe was performed to compare it with a conventional end electrode. It was found that the new pH-probe with circular antimonial electrode for pH measurement at the surface of the mucous coat of upper gastrointestinal tract in a fasting patient considerably increases the accuracy of pH measurement at the site of acid glands. Recommendations for examination of acid-forming and alkalizing functions of stomach and determination of the boundaries of the main regions of stomach during endoscopic examination are given.

Localization of mRNA for the muscarinic M1 receptor in rat stomach.

Cholinergic stimulation of receptors in the oxyntic mucosa results in secretion of mucus, pepsinogen and hydrochloric acid. There has been speculation as to the cellular localization of these receptors in the mucosa and as to which subtype is present in the different cell types. In the present study, utilizing radioactive riboprobes for the M1 muscarinic receptor subtype, we carried out in situ hybridization to determine which cells of the gastric corpus transcribe mRNA for this receptor. The antisense M1 probe hybridized strongly on the zymogen cells and, to a lesser extent, on the surface mucous cells and the muscle layers. Control sections from brain also displayed specific hybridization.

Autoimmune Metaplastic Atrophic Gastritis: Recognizing Precursor Lesions for Appropriate Patient Evaluation.

Autoimmune metaplastic atrophic gastritis (AMAG) is a significant risk factor for pernicious anemia and gastric neoplasia. Still, the histologic features of AMAG are frequently overlooked, especially in the early stages of the disease. The purpose of our study, therefore, was to catalogue the progression of histologic changes that precede the development of AMAG in affected individuals. Over a 2-year period (2012 to 2014), the diagnosis of AMAG was rendered on material from 113 patients seen at Johns Hopkins Hospital (∼1.8% of "in house" gastric biopsies). Prior gastric body biopsies had been performed on 54 (48%) patients in the cohort, and the majority of these specimens had also shown AMAG. Eighteen of the previous biopsies, however, carried a diagnosis other than AMAG: 13 inactive chronic gastritis, 2 acute Helicobacter pylori gastritis, and 1 each of eosinophilic gastritis, iron pill gastritis, and proton-pump inhibitor-like effect. Upon review of these 18 biopsies, the most common histologic findings were heavy full-thickness or deep lamina propria chronic inflammation (12), inflammatory destruction of oxyntic glands (12), metaplasia (intestinal, pyloric, or pancreatic acinar) (10), prominent lamina propria eosinophils (8), and parietal cell pseudohypertrophy (4). At least 2 of these features were present in the majority (13, 72%) of the biopsies. In addition, 7 (58%) of these patients were also found to have another autoimmune or inflammatory disorder before the diagnosis of AMAG. Although subtle, histologic features of developing AMAG are identifiable in routine gastric body biopsies. When metaplasia, full-thickness chronic inflammation, and/or oxyntic destruction are seen, a note suggesting laboratory testing and/or close clinical follow-up in this subset of patients may be warranted.

Oxyntic gland adenoma endoscopically mimicking a gastric neuroendocrine tumor: A case report.

Gastric adenocarcinoma is one of the most common malignancies worldwide. Histochemical and immunohistologic analyses classify the phenotypes of gastric adenocarcinoma into several groups based on the variable clinical and pathologic features. A new and rare variant of gastric adenocarcinoma with chief cell differentiation (GA-CCD) has recently been recognized. Studies reporting the distinct clinicopathologic characteristics proposed the term oxyntic gland polyp/adenoma because of the benign nature of the GA-CCD. Typically, GA-CCD is a solitary mucosal lesion that develops either in the gastric cardia or fundus. Histologically, this lesion is characterized by tightly clustered glands and anastomosing cords of chief cells. Immunohistochemically, GA-CCD is diffusely positive for mucin (MUC) 6 and negative for MUC2 and MUC5AC. However, other gastric tumors such as a gastric neuroendocrine tumor or fundic gland polyp have been difficult to exclude. Because GA-CCD tends to be endoscopically misdiagnosed as a neuroendocrine tumor or fundic gland polyp, comprehensive assessment and observation by an endoscopist are strongly recommended. Herein, we report a rare case of oxyntic gland adenoma endoscopically mimicking a gastric neuroendocrine tumor that was successfully removed by endoscopic mucosal resection.

Identification of ADAM 31: a protein expressed in Leydig cells and specialized epithelia.

A family of proteins containing a disintegrin and metalloproteinase domain (ADAMs) has been identified recently. Here, we report the identification of a novel member of the ADAM protein family from mouse. This protein is designated ADAM 31. The complementary DNA sequence of ADAM 31 predicts a transmembrane protein with metalloproteinase, disintegrin, cysteine-rich, and cytoplasmic domains. Messenger RNA encoding ADAM 31 was most abundant in testes, but was also detected in many other tissues. More significantly, the antibodies raised against ADAM 31 reveal that the protein has a unique and restricted expression pattern. ADAM 31 is expressed in Leydig cells of the testes, but unlike many other ADAMs, it is not found on developing sperm. Furthermore, ADAM 31 is highly expressed on four types of specialized epithelia: the cauda epididymidis, the vas deferens, the convoluted tubules of the kidney, and the parietal cells of the stomach.

Cellular distribution of prolactin receptors in human digestive tissues.

In the present study we analyzed the expression of prolactin receptors (PRLR) in human digestive tissues by immunohistochemistry. PRLR immunoreactivity was primarily localized in the cytoplasm. However, in some organs (liver and salivary glands) a nuclear positivity was also found. The liver was used as control and showed a diffuse immunostaining in the parenchymal cells. In the gastrointestinal tract, PRLR immunoreactivity was observed in the mucosa, muscularis layer, and nervous plexuses. The more intense immunostaining in the mucosa of the different segments was as follows: esophagus, superficial layers of the stratified squamous epithelium and mucous glands; stomach, parietal cells; small intestine, absorptive and Paneth cells; and colon, surface epithelium and superficial half of the crypts of Lieberkühn. In the salivary glands, immunoreactivity was strong in the mucous tubules, moderate in the ducts, and weak in the serous cells. Endocrine pancreas showed a more intense immunoreactivity than the pancreatic acini. By serial sections of the islets of Langerhans we showed that immunostaining was confined to B cells. These findings demonstrate the widespread distribution of PRLR in human digestive tissues and its localization both in cytoplasms and nuclei.

High-resolution immunogold cytochemistry indicates that AQP4 is concentrated along the basal membrane of parietal cell in rat stomach.

Gastric parietal cells secrete hydrochloric acid in stomach. Because the secreted HCl solution is isotonic with the plasma fluid, it should accompany the water transport across the membranes of parietal cells. Aquaporins (AQPs) are water channel proteins that play the central role in the cellular handling of water in various mammalian tissues. Using immunocytochemistry, we found that AQP4 was expressed only in parietal cells of rat gastric mucosa. Immunogold electron microscopy study further demonstrated that AQP4 was mostly localized at the basal membrane of parietal cells. In the basal membrane, AQP4 was prominently enriched on the portion contacting with the basement membrane surrounding gastric glands. These results suggest that the contact between basement membrane and basal membrane may generate the signal involved in the targeting of AQP4 in gastric parietal cells.

Sucrose octasulfate stimulates gastric somatostatin release.

To explore the mechanisms of the effects of sucralfate on the stomach, we investigated the action of sucrose octasulfate (SOS), a constituent of sucralfate, on the function of canine gastric parietal cells and somatostatin cells and in the isolated perfused intact rat stomach. Somatostatin cells from the canine gastric fundus were isolated by EDTA-collagenase dispersion and counterflow elutriation, and somatostatin-like immunoreactivity (SLI) release in response to SOS was measured by radioimmunoassay. Similar methods were used to isolate gastric parietal cells, in which gastric acid secretion was measured by uptake of a radiolabeled weak base, [14C]aminopyrine. SLI release by the intact rat stomach was examined in an isolated vascularly perfused rat stomach model. SOS, either alone or co-administered with epinephrine or gastrin heptadecapeptide (G17), dose-dependently stimulated SLI release by isolated canine fundic D-cells. At the highest doses, SOS potentiated the effect of epinephrine but not G17. Similarly, SOS potentiated the stimulating effect of dibutyryl cyclic adenosine 3',5'-monophosphate (DBcAMP), but not 12-O-tetradecanoylphorbol 13-acetate (TPA). The effect of SOS on SLI release could be inhibited by octreotide, a somatostatin analogue. SOS did not alter acid secretion by cultured canine parietal cells either in the basal state or when coadministered with acid secretagogues. In isolated perfused rat stomach studies, SOS produced a significant (60% greater than basal) increase in SLI secretion. There was a similar effect when SOS was perfused against a background of isoproterenol. SOS stimulates SLI release from gastric somatostatin cells and from the isolated perfused stomach but has no direct effect on gastric parietal cells. These actions of SOS may mediate in part the apparent ability of sucralfate to enhance gastric mucosal defense.

Histamine-storing cells in the oxyntic mucosa of the rat stomach: a transmission electron microscopic study employing fixation with carbodiimide.

We studied the distribution of histamine (HA) immunoreactivity in endocrine cells of the acid-producing mucosa in rat stomach with pre-embedding immunoelectron microscopy (IEM) using an antiserum against HA. Four fixation modifications were compared to optimize the ultrastructural morphology and staining pattern with the antisera produced against carbodiimide-conjugated HA. Fixation with 4% 1-ethyl-3(3-dimethyl-aminopropyl) carbodiimide (EDCDI) combined with both 4% paraformaldehyde and 0.1% glutaraldehyde gave superior results compared with EDCDI alone. Enterochromaffin-like (ECL) cells were easily distinguished from other endocrine cells in optimally fixed samples. The peroxidase end-product was distributed within the cytoplasm surrounding the vesicles of the ECL cells. ECL cells comprised about 75% of all endocrine cells, and about 90% of them were HA immunoreactive (HA-IR). No other HA-IR cell types were identified by EM in the basal half of the oxyntic region of rat gastric mucosa. The results suggest that a combination of EDCDI and aldehydes is suitable for IM demonstration of HA in cells. ECL cells from a predominant portion of endocrine cells in the oxyntic glands and may constitute the only significant non-mast cell store of HA in rat gastric mucosa.

Pharmacological analysis of the muscarinic receptors involved when McN-A 343 stimulates acid secretion in the mouse isolated stomach.

In view of the recent M1 and M2 subclassification of muscarinic receptors and the suggestion of separate populations of muscarinic receptors on oxyntic and histamine cells in the gastric mucosa, we have analysed the effects of McN-A 343, classified as an M1-selective agonist, on gastric acid secretion by the mouse, isolated, lumen-perfused stomach assay. Acid secretion stimulated by McN-A 343 was not inhibited by tetrodotoxin pretreatment, although it was competitively antagonized by atropine (pKB 7.90), suggesting a muscarinic site of action between postganglionic neurones and the final secretory event. Acid secretion stimulated by McN-A 343 was more sensitive than 5-methylfurmethide-stimulated secretion to H2-receptor blockade: the profile of inhibition was consistent with expectations for a model of indirect agonism, suggesting that McN-A 343 preferentially stimulated the release of endogenous histamine from mucosal histamine cells. In view of this selective action the McN-A 343-pirenzepine interaction was studied, the latter being classified as an M1-selective antagonist. Results were consistent with expectations for a competitive interaction but the pKB (6.69) was not significantly different from the value obtained at the oxyntic cell, using 5-methylfurmethide as agonist in the presence of H2-receptor blockade, in a previous study. We suggest that there is no need to postulate differences in oxyntic and histamine cell muscarinic receptors to account for the selective stimulant activity of McN-A 343 observed in this study and the relatively selective inhibition of gastric acid secretion by pirenzepine in vivo. McN-A 343 selectivity may be accounted for by a higher muscarinic receptor density on the histamine cell and pirenzepine selectivity by a smaller degree of loss into the gastric secretion compared to atropine.

Effects on the rat oxyntic mucosa of the histamine2-antagonist loxtidine and the H+, K(+)-ATPase inhibitor omeprazole.

The present study examined whether histamine could affect the growth of the enterochromaffin-like (ECL) cell and the parietal cell. The effects of the unsurmountable histamine H2-receptor antagonist loxtidine (80 mg/kg) and the H+, K(+)-ATPase inhibitor omeprazole (100 mumol/kg) were compared in female Sprague-Dawley rats. Both drugs were given by gavage once daily for 3 months. Omeprazole induced a more pronounced and sustained hypergastrinaemia than loxtidine. In spite of marked hypergastrinaemia during most of the day, even in the loxtidine-treated rats, the weights of the stomach and oxyntic mucosa were elevated only in the omeprazole-treated rats. The ECL cell density was slightly higher in the loxtidine- than in the omeprazole-treated rats. Both treatments elevated the gastrin-stimulated histamine release from the vascularly perfused stomach. The parietal cell density was unaffected by omeprazole treatment, whereas it tended to be reduced in the loxtidine-treated rats. Simultaneous administration of loxtidine and omeprazole reduced the sustained hypergastrinaemia induced by omeprazole given alone. The present study may indicate that histamine inhibits the growth of the ECL cell, but further studies are needed to elucidate if histamine has any trophic effect on the parietal cells.