| 1. |
- Ericson, Ann-Charlott, 1965-, et al.
(författare)
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Morphological examination of the termination pattern of substance P-immunoreactive nerve fibers in human antral mucosa
- 2002
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 107:1-3, s. 79-86
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Tidskriftsartikel (refereegranskat)abstract
- The termination pattern of substance P (SP)-containing axons in human antral mucosa was examined using immunohistochemical techniques at the light and electron microscopic level. SP-immunoreactive (IR) axons were found to extend towards the pit region of the glands, where intraepithelial axons were observed. Electron microscopy showed immunostained axon profiles in close contact with the basement membrane of surface mucous cells. Membrane-to-membrane contacts between labeled axons and myofibroblast-like cells were identified, and SP-IR axons that were apposed to the epithelium were also in contact with subjacent myofibroblast-like cells. The anatomical relationship between SP-IR axons and the cells of the muscularis mucosae was investigated by light microscopy. Immunoreactivity for a-smooth muscle actin (a-sma) was used to visualize the smooth muscle cells, and the a-sma-IR cells were found to create a network that surrounded the gastric glands. Immunostained varicose axons ran alongside and in close apposition to the labeled muscle strands. Ultrastructural examination showed close contacts between SP-IR axon profiles and smooth muscle-like cells. In conclusion, SP-containing neurons may be important for sensory and secretomotor functions in the human antral mucosa.
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| 2. |
- Berg, Anna, 1975-, et al.
(författare)
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Effect of nitric oxide on histamine-induced cytological transformations in parietal cells in isolated human gastric glands
- 2007
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Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 52:1, s. 126-136
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that nitric oxide (NO) inhibits histamine-induced gastric acid secretion in isolated human gastric glands. NO synthase has been found to be present in the human oxyntic mucosa and has been suggested to serve as a paracrine regulator of gastric acid secretion. Histamine stimulation of parietal cells induces cytoskeletal rearrangements, recruitment of H +/K +-ATPase-rich tubulovesicles to the apical membrane and expansion of intracellular canaliculi. The aim of the present study was thus to investigate (i) the effect of an NO donor on histamine-induced cytological transformations and (ii) the influence of increased [Ca 2+] i on NO-induced morphological changes in human parietal cells. Human gastric glands were isolated and subjected to the NO donor SNAP prior to histamine administration. [Ca 2+] i was increased by photolysis of the caged Ca 2+ compound NP-EGTA. The distribution of F-actin, ezrin, and H +/K +-ATPase was assessed by confocal microscopy. Ultrastructural analysis was performed using transmission electron microscopy. SNAP did not influence the histamine-induced translocation of F-actin, ezrin, and H +/K +-ATPase but prevented an increase in the canalicular size. Elevation of [Ca 2+] i in resting cells was found to mimic histamine-induced intraparietal cell transformations; however, NO-induced parietal cell morphology was unaffected by a rise in [Ca 2+] i. These results indicate that NO inhibits secretion of fluid into the canalicular lumen without affecting membrane recruitment and that this effect is Ca 2+-insensitive. © 2006 Springer Science+Business Media, Inc.
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| 3. |
- Berg, Anna, 1975-, et al.
(författare)
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Morphological support for paracrine inhibition of gastric acid secretion by nitric oxide in humans
- 2001
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 36:10, s. 1016-1021
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Tidskriftsartikel (refereegranskat)abstract
- Background: Functional studies have shown that nitric oxide (NO) inhibits gastric acid secretion in a variety of species, including man. We have performed a morphological study with the intention of localizing the endothelial NO synthase (eNOS) in the human gastric mucosa.Methods: Fifteen healthy subjects voluntarily participated in the study, and mucosal biopsies were obtained from the cardia, corpus and antrum. The presence and localization of eNOS were studied using immunohistochemical techniques.Results: eNOS-immunoreactivity (eNOS-IR) is found in surface mucous cells of cardia, corpus and antrum. Unique to the oxyntic mucosa is the presence of eNOS-IR in 'endocrine-like' cells, found in close contact with parietal cells.Conclusions: eNOS-IR cells in close apposition to parietal cells provide morphological support for paracrine inhibition of gastric acid secretion by NO.
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| 4. |
- Berg, Anna, 1975-, et al.
(författare)
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Nitric oxide-an endogenous inhibitor of gastric acid secretion in isolated human gastric glands
- 2004
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Ingår i: BMC Gastroenterology. - 1471-230X. ; 4:16
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEndothelial nitric oxide synthase (eNOS) has previously been detected in the glandular part of the human gastric mucosa. Furthermore, nitric oxide (NO) has been shown to influence gastric secretion in various animal models. The present study was conducted to investigate the influence of exogenously and endogenously derived NO on histamine- and cAMP-stimulated gastric acid secretion in isolated human oxyntic glands.MethodsOxyntic glands were isolated from human gastric biopsies and were subsequently pre-treated with NO donors and nitric oxide synthase inhibitors and then exposed to histamine or dibutyryl-cAMP (db-cAMP). The secretory response of the glands was determined as accumulation of [14C]aminopyrine.ResultsThe histamine- or db-cAMP-induced acid secretion was attenuated by L-arginine, a known source of endogenous NO, and also by the NO-donors sodium nitroprusside (SNP) and S-nitroso-N-acetyl-penicillamine (SNAP). Pre-treatment with either of the NOS inhibitors NG-nitro-L-arginine methyl ester (L-NAME) or NG-nitro-L-arginine (L-NNA) enhanced the secretory response.ConclusionOur results show that NO inhibits gastric acid secretion in isolated human gastric glands, and that there is endogenous formation of NO within the glandular epithelium in the vicinity of the parietal cells.
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| 5. |
- Berg, Anna, 1975-, et al.
(författare)
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Nitric oxide inhibits gastric acid secretion by increasing intraparietal cell levels of cGMP in isolated human gastric glands
- 2005
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 289:6, s. G1061-G1066
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Tidskriftsartikel (refereegranskat)abstract
- We have previously identified cells containing the enzyme nitric oxide (NO) synthase (NOS) in the human gastric mucosa. Moreover, we have demonstrated that endogenous and exogenous NO has been shown to decrease histamine-stimulated acid secretion in isolated human gastric glands. The present investigation aimed to further determine whether this action of NO was mediated by the activation of guanylyl cyclase (GC) and subsequent production of cGMP. Isolated gastric glands were obtained after enzymatic digestion of biopsies taken from the oxyntic mucosa of healthy volunteers. Acid secretion was assessed by measuring [14C]aminopyrine accumulation, and the concentration of cGMP was determined by radioimmunoassay. In addition, immunohistochemistry was used to examine the localization of cGMP in mucosal preparations after stimulation with the NO donor S-nitroso-N-acetylpenicillamine (SNAP). SNAP (0.1 mM) was shown to decrease acid secretion stimulated by histamine (50 μM); this effect was accompanied by an increase in cGMP production, which was histologically localized to parietal cells. The membrane-permeable cGMP analog dibuturyl-cGMP (db-cGMP; 0.1–1 mM) dose dependently inhibited acid secretion. Additionally, the effect of SNAP was prevented by preincubating the glands with the GC inhibitor 4H-8-bromo-1,2,4-oxadiazolo[3,4-d]benz[b][1,4]oxazin-1-one (10 μM). We therefore suggest that NO in the human gastric mucosa is of physiological importance in regulating acid secretion. Furthermore, the results show that NO-induced inhibition of gastric acid secretion is a cGMP-dependent mechanism in the parietal cell involving the activation of GC.
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| 6. |
- Svedhem, Sofia, et al.
(författare)
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Subtle differences in dissociation rates of interactions between destabilized human carbonic anhydrase II mutants and immobilized benzenesulfonamide inhibitors probed by a surface plasmon resonance biosensor
- 2001
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 296:2, s. 188-196
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Tidskriftsartikel (refereegranskat)abstract
- The development of commercial biosensors based on surface plasmon resonance has made possible careful characterization of biomolecular interactions. Here, a set of destabilized human carbonic anhydrase II (HCA II) mutants was investigated with respect to their interaction kinetics with two different immobilized benzenesulfonamide inhibitors. Point mutations were located distantly from the active site, and the destabilization energies were up to 23 kJ/mol. The dissociation rate of wild-type HCA II, as determined from the binding to the inhibitor with higher affinity, was 0.019 s−1. For the mutants, dissociation rates were faster (0.022–0.025 s−1), and a correlation between faster dissociation and a high degree of destabilization was observed. We interpreted these results in terms of increased dynamics of the tertiary structures of the mutants. This interpretation was supported by entropy determinations, showing that the entropy of the native structure significantly increased upon destabilization of the protein molecule. Our findings demonstrate the applicability of modern biosensor technology in the study of subtle details in molecular interaction mechanisms, such as the long-range effect of point mutations on interaction kinetics.
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