Article

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: 3.74). 08/2008; 295(4):G671-81. DOI: 10.1152/ajpgi.90224.2008
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
134 Views
  • [Show abstract] [Hide abstract]
    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.
    Biochemical and Biophysical Research Communications 03/2014; 447(1). DOI:10.1016/j.bbrc.2014.03.095 · 2.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This article offers an explanation for the apparent lack of Na, K-ATPase activity in parietal cells although ouabain has been known to inhibit gastric acid secretion since 1962. The gastric H, K-ATPase (proton-pump) seems to be acting in altered states, thus behaving like a Na, K-ATPase (Na-pump) and/or Ca-ATPase (Ca-pump) depending on cellular needs. This conclusion is based on the following findings. First, parietal cell fractions do not exhibit Na, K-ATPase activity at pH 7.0 but do at pH 8.5. Second, the apical plasma membrane (APM) fraction exhibits a (Ca or Mg)-ATPase activity with negligible H, K-ATPase activity. However, when assayed with Mg alone in presence of the 80 k Da cytosolic proton-pump activator (HAF), the APM fraction reveals remarkably high H, K-ATPase activity, suggesting the observed low affinity of Ca (or Mg)-ATPase is an altered state of the latter. Third, calcium (between 1 and 4 µM) shows both stimulation and inhibition of the HAF-stimulated H, K-ATPase depending on its concentration, revealing a close interaction between the proton-pump activator and local Ca concentration in gastric H, K-ATPase function. Such interactions suggest that Ca is acting as a terminal member of the intracellular signaling system for the HAF-regulated proton-pump. It appears that during resting state, the HAF-associated H, K-ATPase remains inhibited by Ca (>1 µM) and, prior to resumption of acid secretion the gastric H, K-ATPase acts temporarily as a Ca-pump for removing excess Ca from its immediate environment. This conclusion is consistent with the recent reports of immunochemical co-localization of the gastric H, K-ATPase and Ca-ATPase by superimposition in parietal cells, and a transitory efflux of Ca immediately preceding the onset of acid secretion. These new perspectives on proton-pump function would open new avenues for a fuller understanding of the intracellular regulation of the ubiquitous Na-pump.
    01/2013; 2:165. DOI:10.12688/f1000research.2-165.v1
  • Source
    [Show abstract] [Hide abstract]
    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.
    Advances in Pharmacological Sciences 02/2014; 2014:323470. DOI:10.1155/2014/323470