Perez-Zoghbi JF, Mayora A, Ruiz MC, Michelangeli F. Heterogeneity of acid secretion induced by carbachol and histamine along the gastric gland axis and its relationship to [Ca2+]i

Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
AJP Gastrointestinal and Liver Physiology (Impact Factor: 3.8). 08/2008; 295(4):G671-81. DOI: 10.1152/ajpgi.90224.2008
Source: PubMed


The gastric glands of the mammalian fundic mucosa are constituted by different cell types. Gastric fluid is a mixture of acid, alkali, ions, enzymes, and mucins secreted by parietal, chief, and mucous cells. We studied activation of acid secretion using LysoSensor Yellow/Blue in conjunction with fluo 3 to measure changes in pH and Ca(2+) in isolated rabbit gastric glands. We evidenced a spatial heterogeneity in the amplitude of acid response along the gland axis under histamine and cholinergic stimulation. Carbachol induced a transitory pH increase before acidification. This relative alkalinization may be related to granule release from other cell types. Omeprazole inhibited the acid component but not the rise in pH. Histamine stimulated acid secretion without increase of lumen pH. We studied the relationship between Ca(2+) release and/or entry and H(+) secretion in glands stimulated by carbachol. Ca(2+) release was associated with a fast and transient components of H(+) secretion. We found a linear relationship between Ca(2+) release and H(+) secretion. Ca(2+) entry was associated with a second slow and larger component of acid secretion. The fast component may be the result of activation of Cl(-) and K(+) channels and hence H(+)/K(+) pumps already present in the membrane, whereas the slow component might be associated with translocation of H(+)/K(+) pumps to the canaliculi. In conclusion, with cholinergic stimulation, gastric glands secrete a mixture of acid and other product(s) with a pH above 4.2, both triggered by Ca(2+) release. Maintenance of acid secretion depends on Ca(2+) entry and perhaps membrane fusion.

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Available from: Fabian Michelangeli, Nov 17, 2015
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    • "Moreover, identifying the location of the cells in their living state is difficult, as immunostaining and scanning electron microscopic (SEM) observations require fixation of the gastric gland. Some researchers use the gastric gland model [2]; however, coordinated secretion in living gastric glands has rarely been studied [3]. In order to determine the types of cells that participate in group activities, we developed a simple method to identify parietal cells in living gastric glands and demonstrate the coordinated activity of these cells. "
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    ABSTRACT: Secretion from the gastric gland involves the activation of various types of cells in a coordinated manner. In order to elucidate the mechanisms underlying the coordination of secretion, we studied live fluorescence images of guinea pig gastric glands stained with acridine orange (AO). On 2 μM AO staining, individual cells were characterized by metachromatic colors and various intensities of fluorescence. When the gland was stimulated with 100 μM of histamine, green fluorescence was transiently increased in parietal cells and intermediate cells and propagated along the gland for a long distance over many cells. Local stimulation in a couple of cells with histamine in the presence of suramin also induced propagation. However, the fluorescence response was suppressed by the addition of H-89, a protein kinase A inhibitor. These findings suggest that a cAMP-dependent signal propagates intercellularly through a variety of cells to induce coordinated secretion in the entire gastric gland.
    Preview · Article · Mar 2014 · Biochemical and Biophysical Research Communications
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    • "g) compared with the controls (45.04 g) (Table 1). Pepsin inactivation occurs at about pH 6. Between pH 4 and 6, pepsin is still stable but inactive [45]. Gastric pH values obtained in all the experiments in response to extract administration ranged between 3.97 and 5.26, suggesting that the extract may deactivate gastric pepsin and interfere with protein digestion. "
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    ABSTRACT: Objective. The objective of this study was to find out the possible antiulcer mechanism of action of Eremomastax speciosa. Method. Carbachol- and histamine-induced hypersecretion, associated with the pylorus ligation technique, were used in rats. Gastric mucosal ulceration, mucus production, pH, gastric volume, and acidity were measured. Results. Histamine and carbachol raised gastric acidity to 86.50 and 84.80 mEq/L, respectively, in the control rats, and the extracts (200 mg/kg) reduced gastric acidity to 34.60 and 39.00 mEq/L, respectively. Intraduodenal aqueous extract (400 mg/kg) in histamine- and carbachol-treated rats produced significant (P < 0.001) decreases in acid secretion to 28.50 and 28.80 mEq/L, respectively, and 100 percent inhibition of gastric ulceration. Augmented histamine-induced gastric acid secretion (90.20 mEq/L) was significantly reduced to 52.60 and 27.50 mEq/L by the 200 and 400 mg/kg doses of the aqueous extract, respectively. The extract significantly reduced (P < 0.001) the volume of gastric secretion and significantly increased mucus production. The ulcer inhibition potential of the extract significantly dropped to 25-44% (oral extract) and to 29-37% (duodenal extract) in carbachol/indomethacin-treated rats. Conclusion. The aqueous extract of E. speciosa has both cytoprotective and antisecretory effects. The antisecretory effect may involve a mechanism common to both cholinergic and histaminergic pathways.
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    • "This potential relationship between Zn and Ca2+ levels may in part explain the role of Zn and Zn transporters in the intestinal secretion (Liu et al. 2011). Based on the well-recognized role of Ca2+ as a second messenger in responses to secretagogues (Caroppo et al. 2001; Perez-Zoghbi et al. 2008), there is a novel concept that Ca2+ may be also a second messenger that can match the basolateral demand for Zn with the secretory response to physiologic stimulation (Liu et al. 2011). Similar connections may be also present in other secretory cells including neural, endocrine, and exocrine tissues. "
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    ABSTRACT: The SLC30 family of divalent cation transporters is thought to be involved in the transport of zinc in a variety of cellular pathways. Zinc transporter 3 (ZnT3) is involved in the transport of zinc into synaptic vesicles or intracellular organelles. As the presence of ZnT3 immunoreactive neurons has recently been reported in both the central and peripheral nervous systems of the rat, the present study was aimed at disclosing the presence of a zinc-enriched neuron enteric population in the porcine duodenum to establish a preliminary insight into their neurochemical coding. Double- and triple-immunofluorescence labeling of the porcine duodenum for ZnT3 with the pan-neuronal marker (PGP 9.5), substance P, somatostatin, vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS), leu-enkephalin, vesicular acetylcholine transporter (VAChT), neuropeptide Y, galanin (GAL), and calcitonin gene-related peptide were performed. Immunohistochemistry revealed that approximately 35, 43, and 48 % of all PGP9.5-postive neurons in the myenteric (MP), outer submucous (OSP), and inner submucous (ISP) plexuses, respectively, of the porcine duodenum were simultaneously ZnT3(+). In the present study, ZnT3(+) neurons coexpressed a broad spectrum of active substances, but co-localization patterns unique to the plexus were studied. In the ISP, all ZnT3(+) neurons were VAChT positive, and the largest populations among these cells formed ZnT3(+)/VAChT(+)/GAL(+) and ZnT3(+)/VAChT(+)/VIP(+) cells. In the OSP and MP, the numbers of ZnT3(+)/VAChT(+) neurons were two times smaller, and substantial subpopulations of ZnT3(+) neurons in both these plexuses formed ZnT3(+)/NOS(+) cells. The large population of ZnT3(+) neurons in the porcine duodenum and a broad spectrum of active substances which co-localize with this peptide suggest that ZnT3 takes part in the regulation of various processes in the gut both in normal physiology and during pathological processes.
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