| 1. |
- Bengtsson, Magnus W., et al.
(author)
-
Food-induced expression of orexin receptors in rat duodenal mucosa regulates the bicarbonate secretory response to orexin-A
- 2007
-
In: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 293:2, s. G501-G509
-
Journal article (peer-reviewed)abstract
- Presence of appetite-regulating peptides orexin-A and orexin-B in mucosal endocrine cells suggests a role in physiological control of the intestine. Our aim was to characterize orexin-induced stimulation of duodenal bicarbonate secretion and modulation of secretory responses and mucosal orexin receptors by overnight food deprivation. Lewis x Dark Agouti rats were anesthetized and proximal duodenum cannulated in situ. Mucosal bicarbonate secretion (pH stat) and mean arterial blood pressure were continuously recorded. Orexin-A was administered intra-arterially close to the duodenum, intraluminally, or into the brain ventricles. Total RNA was extracted from mucosal specimens, reverse transcribed to cDNA and expression of orexin receptors 1 and 2 (OX1 and OX2) measured by quantitative real-time PCR. OX1 protein was measured by Western blot. Intra-arterial orexin-A (60–600 nmol·h–1·kg–1) increased (P < 0.01) the duodenal secretion in fed but not in fasted animals. The OX1 receptor antagonist SB-334867, which was also found to have a partial agonist action, abolished the orexin-induced secretory response but did not affect secretion induced by the muscarinic agonist bethanechol. Atropine, in contrast, inhibited bethanechol but not orexin-induced secretion. Orexin-A infused into the brain ventricles (2–20 nmol·kg–1·h–1) or added to luminal perfusate (1.0–100 nM) did not affect secretion, indicating that orexin-A acts peripherally and at basolateral receptors. Overnight fasting decreased mucosal OX1 and OX2 mRNA expression (P < 0.01) as well as OX1 protein expression (P < 0.05). We conclude that stimulation of secretion by orexin-A may involve both receptor types and is independent of cholinergic pathways. Intestinal OX receptors and secretory responses are markedly related to food intake.
|
|
| 2. |
- Bengtsson, Magnus W., et al.
(author)
-
Short food deprivation inhibits orexin receptor 1 expression and orexin-A induced intracellular calcium signaling in acutely isolated duodenal enterocytes
- 2009
-
In: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 296:3, s. G651-G658
-
Journal article (peer-reviewed)abstract
- Bengtsson MW, Makela K, Herzig KH, Flemstrom G. Short food deprivation inhibits orexin receptor 1 expression and orexin-A induced intracellular calcium signaling in acutely isolated duodenal enterocytes. Am J Physiol Gastrointest Liver Physiol 296: G651-G658, 2009. First published December 31, 2008; doi:10.1152/ajpgi.90387.2008.-Close intra-arterial infusion of the appetite regulating peptide orexin-A stimulates bicarbonate secretion from the duodenal mucosa. The aim of the present study was to elucidate the ability of orexin-A to induce intracellular calcium signaling in acutely isolated duodenal enterocytes. Freshly isolated clusters of enterocytes, obtained from rat duodenal mucosa or human duodenal biopsies, were loaded with fura 2-AM and mounted in a perfusion chamber. Cryptlike enterocytes were selected (caged), and changes in intracellular calcium concentration ([Ca2+](i)) were evaluated by fluorescence imaging. Total RNA was extracted from pellets of enterocytes and reverse transcribed to cDNA, and expression of orexin receptors 1 and 2 (OX1R and OX2R) was measured by quantitative real-time PCR. Orexin-A at all concentrations tested (1-100 nM) increased [Ca2+](i) in enterocytes isolated from continuously fed rats, and the OX1R-antagonist SB-334867 (10 nM) attenuated the response. The primary [Ca2+](i) response was a slow increase to a sustained plateau persisting after orexin-A removal, and a similar response was observed in enterocytes from human biopsies. In contrast to orexin-A, the OX2R agonist (Ala(11), D-Leu(15))orexin-B (1-10 nM) did not induce calcium signaling. There were no significant [Ca2+](i) responses in enterocytes from animals food deprived overnight, and overnight fasting decreased (P < 0.01) enterocyte OX1R as well as OX2R mRNA. Induction of intracellular calcium signaling in isolated duodenal enterocytes is thus mediated primarily by OX1R receptors. Short (overnight) food deprivation markedly depresses receptor expression and inhibits orexin-A induced increases in [Ca2+](i). Studies of enterocyte signaling and intestinal secretion requires particular evaluation regarding feeding status.
|
|
| 3. |
- Berg, Anna, 1975-, et al.
(author)
-
Nitric oxide inhibits gastric acid secretion by increasing intraparietal cell levels of cGMP in isolated human gastric glands
- 2005
-
In: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 289:6, s. G1061-G1066
-
Journal article (peer-reviewed)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.
|
|
| 4. |
- Canny, G, et al.
(author)
-
Functional and biochemical characterization of epithelial bactericidal/permeability-increasing protein
- 2006
-
In: American Journal of Physiology: Gastrointestinal and Liver Physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 290:3, s. 557-567
-
Journal article (peer-reviewed)abstract
- Epithelial cells of many mucosal organs have adapted to coexist with microbes and microbial products. In general, most studies suggest that epithelial cells benefit from interactions with commensal microorganisms present at the lumenal surface. However, potentially injurious molecules found in this microenvironment also have the capacity to elicit local inflammatory responses and even systemic disease. We have recently demonstrated that epithelia cells express the anti-infective molecule bactericidal/permeability-increasing protein (BPI). Here, we extend these findings to examine molecular mechanisms of intestinal epithelial cell (IEC) BPI expression and function. Initial experiments revealed a variance of BPI mRNA and protein expression among various IEC lines. Studies of BPI promoter expression in IECs identified regulatory regions of the BPI promoter and revealed a prominent role for CCAAT/enhancer binding protein and especially Sp1/Sp3 in the basal regulation of BPI. To assess the functional significance of this protein, we generated an IEC line stably transfected with full-length BPI. We demonstrated that, whereas epithelia express markedly less BPI protein than neutrophils, epithelial BPI contributes significantly to bacterial killing and attenuating bacterial-elicted proinflammatory signals. Additional studies in murine tissue ex vivo revealed that BPI is diffusely expressed along the crypt-villous axis and that epithelial BPI levels decrease along the length of the intestine. Taken together, these data confirm the transcriptional regulation of BPI in intestinal epithelia and provide insight into the relevance of BPI as an anti-infective molecule at intestinal surfaces.
|
|
| 5. |
- Casselbrant, Anna, 1970, et al.
(author)
-
Angiotensin II receptors are expressed and functional in human esophageal mucosa.
- 2009
-
In: American journal of physiology. Gastrointestinal and liver physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 297:5
-
Journal article (peer-reviewed)abstract
- Only few studies have been devoted to the actions of the renin-angiotensin system (RAS) in the human gastrointestinal tract. The present study was undertaken to elucidate the expression and action of RAS in the human esophageal mucosa. Mucosal specimens with normal histological appearance were obtained from healthy subjects undergoing endoscopy and from patients undergoing esophagectomy due to neoplasm. Gene and protein expressions of angiotensin II (Ang II) receptor type 1 (AT(1)) and type 2 (AT(2)) and angiotensin-converting enzyme (ACE) were analyzed. In vivo functionality in healthy volunteers was reflected by assessing transmucosal potential difference (PD). Ussing chamber technique was used to analyze the different effects of Ang II on its AT(1) and AT(2) receptors. Immunoreactivity to AT(1) and AT(2) was localized to stratum superficiale and spinosum in the epithelium. ACE, AT(1), and AT(2) were found in blood vessel walls. Transmucosal PD in vivo increased following administration of the AT(1) receptor antagonist candesartan. In Ussing preparations mean basal transmural PD was -6.4 mV, epithelial current (I(ep)) 34 muA/cm(2), and epithelial resistance (R(ep)) 321 Omega.cm(2). Serosal exposure to Ang II increased PD as a result of increased I(ep), whereas R(ep) was constant. Ang II given together with the selective AT(1)-receptor antagonist losartan, or AT(2) agonist C21 given alone, resulted in a similar effect. Ang II given in presence of the AT(2)-receptor antagonist PD123319 did not influence PD, but I(ep) decreased and R(ep) increased. In conclusion, Ang II receptors and ACE are expressed in the human esophageal epithelium. The results suggest that AT(2)-receptor stimulation increases epithelial ion transport, whereas the AT(1) receptor inhibits ion transport and increases R(ep).
|
|
| 6. |
- Chen, Duan, et al.
(author)
-
Differentiation of the Gastric Mucosa I. Role of histamine in control of function and integrity of oxyntic mucosa: understanding gastric physiology through disruption of targeted genes
- 2006
-
In: American Journal of Physiology: Gastrointestinal and Liver Physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 291:4, s. 539-544
-
Journal article (peer-reviewed)abstract
- Many physiological functions of the stomach depend on an intact mucosal integrity; function reflects structure and vice versa. Histamine in the stomach is synthesized by histidine decarboxylase (HDC), stored in enterochromaffin-like (ECL) cells, and released in response to gastrin, acting on CCK2 receptors on the ECL cells. Mobilized ECL cell histamine stimulates histamine H-2 receptors on the parietal cells, resulting in acid secretion. The parietal cells express H-2, M-3, and CCK2 receptors and somatostatin sst(2) receptors. This review discusses the consequences of disrupting genes that are important for ECL cell histamine release and synthesis (HDC, gastrin, and CCK2 receptor genes) and genes that are important for "cross-talk" between H-2 receptors and other receptors on the parietal cell (CCK2, M-3, and sst(2) receptors). Such analysis may provide insight into the functional significance of gastric histamine.
|
|
| 7. |
- Flemström, Gunnar, et al.
(author)
-
Epithelial Cells and Their Neighbors : II. New perspectives on efferent signaling between brain, neuroendocrine cells, and gut epithelial cells
- 2005
-
In: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 289:3, s. G377-G380
-
Journal article (peer-reviewed)abstract
- Surface sensory enteroendocrine cells are established mucosal taste cells that monitor luminal contents and provide an important link in transfer of information from gut epithelium to the central nervous system. Recent studies now show that these cells can also mediate efferent signaling from the brain to the gut. Centrally elicited stimulation of vagal and sympathetic pathways induces release of melatonin, which acts at MT(2) receptors to increase mucosal electrolyte secretion. Psychological factors as well mucosal endocrine cell hyperplasia are implicated in functional intestinal disorders. Central nervous influence on the release of transmitters from gut endocrine cells offers an exciting area of future gastrointestinal research with a clinical relevance.
|
|
| 8. |
- Fåk, Frida, et al.
(author)
-
Microbial manipulation of the rat dam changes bacterial colonization and alters properties of the gut in her offspring.
- 2008
-
In: American Journal of Physiology: Gastrointestinal and Liver Physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 294, s. 148-154
-
Journal article (peer-reviewed)abstract
- The impact of an altered bacterial colonization on gut development has not been thoroughly studied, despite the increased risk of certain diseases with a disturbed microbiota after birth. This study was conducted to determine the effect of microbial manipulation, i.e. antibiotic treatment or Escherichia coli (E. coli) exposure, of the dam on bacterial colonization and gut development in the offspring. Pregnant rats were administered either broad-spectrum antibiotics three days prior to parturition, or live non-pathogenic E. coli CCUG 29300T one week before parturition and up to 14 days of lactation in the drinking water. Caecal bacterial levels, gut growth, intestinal permeability, digestive enzyme levels and intestinal inflammation were studied in two-week old rats. Pups from dams that were antibiotic-treated had higher densities of Enterobacteriaceae which correlated with a decreased stomach growth and function, lower pancreatic protein levels, higher intestinal permeability and increased plasma levels of the acute phase protein, haptoglobin, compared with pups from untreated mothers. Exposure of pregnant/lactating mothers to E. coli CCUG 29300T, also resulting in increased Enterobacteriaceae levels, gave in the offspring similar results on the stomach and an increased small intestinal growth as compared to the control pups. Furthermore, E. coli pups showed increased mucosal disaccharidase activities, increased liver, spleen and adrenal weights, as well as increased plasma concentrations of haptoglobin. These findings indicate that disturbing the normal bacterial colonization after birth, by increasing the densities of caecal Enterobacteriaceae, appear to have lasting effects on the postnatal microflora which affects gut growth and function.
|
|
| 9. |
|
|
| 10. |
- Ghanem, E, et al.
(author)
-
Luminal adenosine stimulates chloride secretion through A1 receptor in mouse jejunum
- 2005
-
In: American journal of physiology. Gastrointestinal and liver physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 288:5, s. G972-G977
-
Journal article (peer-reviewed)abstract
- Adenosine is known to stimulate chloride secretion by mouse jejunum. Whereas the receptor on the basolateral side is believed to be A2B, the receptor involved in the luminal effect of adenosine has not been identified. We found that jejuna expressed mRNA for all adenosine receptor subtypes. In this study, we investigated the stimulation of chloride secretion by adenosine in jejuna derived from mice lacking the adenosine receptors of A1(A1R) and A2A(A2AR) or control littermates. The jejunal epithelium was mounted in a Ussing chamber, and a new method on the basis of impedance analysis was used to calculate the short-circuit current ( Isc) values. Chloride secretion was assessed by the Iscafter inhibition of the sodium-glucose cotransporter by adding phloridzin to the apical bathing solution. The effect of apical adenosine on chloride secretion was lost in jejuna from mice lacking the A1R. There was no difference in the response to basolaterally applied adenosine or to apical forskolin. Furthermore, in jejuna from control mice, the effect of apical adenosine was also abolished in the presence of 8-cyclopentyl-1,3-dipropylxanthine, a specific A1R antagonist. Responses to adenosine were identical in jejuna from control and A2AR knockout mice. This study demonstrates that A1R (and not A2AR) mediates the enhancement of chloride secretion induced by luminal adenosine in mice jejunum.
|
|
