PAR-2-mediated control of barrier function and motility differs between early and late phases of postinfectious gut dysfunction in the rat

2013 ◽  
Vol 304 (4) ◽  
pp. G390-G400 ◽  
Author(s):  
Juan A. Fernández-Blanco ◽  
Morley D. Hollenberg ◽  
Vicente Martínez ◽  
Patri Vergara
Keyword(s):  
Ion Transport ◽  
Rat Model ◽  
Barrier Function ◽  
Early Phase ◽  
Trichinella Spiralis ◽  
Late Phase ◽  
Organ Bath ◽  
Motor Responses ◽  
Gut Dysfunction

Proteinase-activated receptor-2 (PAR-2) and mast cell (MC) mediators contribute to inflammatory and functional gastrointestinal disorders. We aimed to characterize jejunal PAR-2-mediated responses and the potential MC involvement in the early and late phases of a rat model of postinfectious gut dysfunction. Jejunal tissues of control and Trichinella spiralis-infected (14 and 30 days postinfection) rats, treated or not with the MC stabilizer, ketotifen, were used. Histopathology and immunostaining were used to characterize inflammation, PAR-2 expression, and mucosal and connective tissue MCs. Epithelial barrier function (hydroelectrolytic transport and permeability) and motility were assessed in vitro in basal conditions and after PAR-2 activation. Intestinal inflammation on day 14 postinfection (early phase) was significantly resolved by day 30 (late phase) although MC counts and epithelial permeability remained increased. PAR-2-mediated ion transport (Ussing chambers, in vitro) and epithelial surface PAR-2 expression were reduced in the early phase, with a trend toward normalization during the late phase. In control conditions, PAR-2 activation (organ bath) induced biphasic motor responses (relaxation followed by excitation). At 14 days postinfection, spontaneous contractility and PAR-2-mediated relaxations were enhanced; motor responses were normalized on day 30. Postinfectious changes in PAR-2 functions were not affected by ketotifen treatment. We concluded that, in the rat model of Trichinella spiralis infection, alterations of intestinal PAR-2 function and expression depend on the inflammatory phase considered. A lack of a ketotifen effect suggests no interplay between MCs and PAR-2-mediated motility and ion transport alterations. These observations question the role of MC mediators in PAR-2-modulating postinfectious gut dysfunction.

Effects of platelet-activating factor on ion transport in isolated rat jejunum

1989 ◽  
Vol 257 (5) ◽  
pp. G845-G850 ◽  
Author(s):  
A. C. Hanglow ◽  
J. Bienenstock ◽  
M. H. Perdue
Keyword(s):  
Ion Transport ◽  
Early Phase ◽  
Short Circuit ◽  
Late Phase ◽  
Platelet Activating Factor ◽  
Short Circuit Current ◽  
Cyclooxygenase Inhibitors ◽  
Base Line ◽  
Intermediate Cell ◽  
Rat Jejunum

In isolated normal rat jejunum, platelet-activating factor (PAF) induced a dose-dependent increase in short-circuit current (Isc) that was reduced in chloride-free buffer and inhibited by the Cl- channel blocker, diphenylamine-2-carboxylate. An immediate rise in Isc (early phase) occurred that fell to a new elevated base line by 15 min (late phase). These responses to PAF occurred only when experiments were conducted at or before approximately 9 A.M. Early phase responses were blocked by the specific PAF antagonists, BN52021 and WEB2086, and were inhibited by the neurotoxin, tetrodotoxin. Early and late phases were also reduced by cyclooxygenase inhibitors and by doxantrazole, a mast cell stabilizing drug. However, histamine and serotonin antagonists were ineffective. We conclude that PAF causes changes in ion transport that include Cl- secretion and acts on the epithelium possibly via an intermediate cell and enteric nerves. In addition, known PAF receptors are involved in one component of the response that appears to follow a circadian rhythm.

16 Differential Effects of PAR-2 Activation on Barrier Function and Motility During Acute and Chronic Inflammation in a Rat Model of Postinfectious Gut Dysfunction

2012 ◽  
Vol 142 (5) ◽  
pp. S-4-S-5
Author(s):  
Joan Antoni Fernandez-Blanco ◽  
Ferran Jardi ◽  
Morley D. Hollenberg ◽  
Vicente Martinez ◽  
Patri Vergara
Keyword(s):  
Chronic Inflammation ◽  
Rat Model ◽  
Barrier Function ◽  
Differential Effects ◽  
Gut Dysfunction ◽  
Acute And Chronic Inflammation

scholarly journals The regulation of growth hormone secretion from the isolated rat anterior pituitary in vitro. The role of adenosine 3′:5′-cyclic monophosphate

1971 ◽  
Vol 124 (4) ◽  
pp. 815-826 ◽  
Author(s):  
R. B. Lockhart Ewart ◽  
K. W. Taylor
Keyword(s):  
Growth Hormone ◽  
Cyclic Amp ◽  
Early Phase ◽  
Late Phase ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Hormone Release ◽  
Dibutyryl Cyclic Amp ◽  
Cyclic Monophosphate

1. The release of growth hormone from isolated fragments of rat anterior pituitary tissue incubated in vitro was studied by employing a double-antibody radioimmunoassay. 2. In the absence of added stimuli, two phases of hormone release could be distinguished, an early phase of 2h duration and a subsequent late phase. In the early phase, hormone release was rapid but could be significantly decreased by calcium depletion and by 2,4-dinitrophenol whereas the rate of release in the late phase was uninfluenced by these incubation conditions. These results have been interpreted as indicating the existence of a secretory component in the early phase of release. 3. In subsequent experiments, the effects of various agents on the rate of hormone output during the late phase of incubation were investigated. Hormone release was increased by theophylline and by dibutyryl cyclic AMP (N6-2′-O-dibutyryl-adenosine 3′:5′-cyclic monophosphate), the response to both of these agents being related to the concentration of the stimulant employed. 4. The stimulation of growth hormone output by theophylline was significantly decreased by calcium deprivation and by 2,4-dinitrophenol. The response to dibutyryl cyclic AMP was diminished by 2,4-dinitrophenol, iodoacetate and 2-deoxyglucose but not by malonate or colchicine. 5. Arginine, β-hydroxybutyrate, albumin-bound palmitate and variation in the glucose concentration of the incubation medium over a wide range were without any statistically significant effect on the rate of hormone release from either control pituitary fragments or those subject to secretory stimulation by dibutyryl cyclic AMP. 6. It is suggested that the regulation of growth hormone secretion is mediated by cyclic AMP (adenosine 3′:5′-cyclic monophosphate). The secretion observed in response to cyclic AMP requires the presence of ionized calcium and a source of metabolic energy but is independent of pituitary protein synthesis de novo. The integrity of the glycolytic pathway of glucose metabolism appears to be essential for cyclic AMP-stimulated growth hormone secretion to occur.

Osmolality affects ion and water fluxes and secretion in the ferret trachea

1993 ◽  
Vol 74 (6) ◽  
pp. 2788-2794 ◽  
Author(s):  
A. M. Price ◽  
S. E. Webber ◽  
J. G. Widdicombe
Keyword(s):  
Ion Transport ◽  
Active Transport ◽  
Organ Bath ◽  
Water Fluxes ◽  
Blue Dextran ◽  
Submucosal Glands ◽  
Active Ion Transport ◽  
Hyperosmolar Solutions ◽  
Active Processes

Nonisosmolar solutions were placed in the lumen of the ferret trachea in vitro in an organ bath. Hyposmolar (150 mmol/kg) solutions progressively increased in osmolarity over 1 h. Increases in luminal concentration of impermeant blue dextran occurred only after 5 min, suggesting that the initial changes were due to ion rather than water fluxes. With hyperosmolar solutions the osmolarity decreased over 1 h with no change in blue dextran concentration, indicating that ion but not water fluxes were taking place. Cooling the preparation to 4 degrees C greatly reduced the osmolaity changes with hyperosmolar solutions and halved those with hyposmolar solutions, suggesting that active ion transport was involved. Hyposmolar (75–150 mmol/kg) and hyperosmolar (450–900 mmol/kg) solutions both increased albumin output into the lumen, but the response was prevented by cooling the trachea to 4 degrees C. Hyposmolar and hyperosmolar solutions both increased the output of lysozyme from glandular serous cells into the lumen. The response to hyposmolar solutions was stronger. Cooling the trachea abolished the lysozyme response to hyperosmolar solutions. Thus hypo- and hyperosmolar solutions promote ion transport in directions to restore isosmolarity. Both nonisosmolar solutions promote albumin movement by active transport across the mucosa and lysozyme secretion from submucosal glands, responses inhibited by tracheal cooling and therefore dependent on metabolically active processes.

scholarly journals Role of Egr1 on Pancreatic Endoderm Differentiation

Cell Medicine ◽  
2018 ◽  
Vol 10 ◽  
pp. 215517901773317
Author(s):  
Takako Tsugata ◽  
Naruo Nikoh ◽  
Tatsuya Kin ◽  
Chika Miyagi-Shiohira ◽  
Yoshiki Nakashima ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Early Phase ◽  
Late Phase ◽  
Embryonic Stem ◽  
Clinical Implementation ◽  
Insulin Producing Cells ◽  
Low Efficiency

The low efficiency of in vitro differentiation of human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (iPSCs) into insulin-producing cells is a crucial hurdle for the clinical implementation of human pluripotent stem cells (PSCs). Our previous investigation into the key factors for the differentiation of PSCs into insulin-producing cells suggested that the expression of GATA binding protein 6 (GATA6) and Gremlin 1 (GREM1) and inhibition of early growth response protein 1 (Egr1) may be important factors. In this study, we investigated the role of Egr1 in pancreas development. The transfection of small interfering RNA (siRNA) of Egr1 in the early phase induced the differentiation of iPSCs derived from fibroblasts (FiPSCs) into pancreatic endoderm and insulin-producing cells. In contrast, the downregulation of Egr1 in the late phase suppressed the differentiation of FiPSCs into pancreatic endoderm and insulin-producing cells. In addition, the overexpression of Egr1 suppressed the differentiation of iPSCs derived from pancreatic cells into pancreatic endoderm and insulin-producing cells. These data suggest that the downregulation of Egr1 in the early phase can efficiently induce the differentiation of iPSCs into insulin-producing cells.

scholarly journals Neutrophils Play an Essential Role in Cooperation with Antibody in both Protection against and Recovery from Pulmonary Infection with Influenza Virus in Mice

2008 ◽  
Vol 82 (6) ◽  
pp. 2772-2783 ◽  
Author(s):  
Haruo Fujisawa
Keyword(s):  
Influenza Virus ◽  
Early Phase ◽  
Influenza A ◽  
Essential Role ◽  
Late Phase ◽  
Passive Transfer ◽  
Plateau Phase ◽  
Virus Propagation ◽  
Virus Elimination

ABSTRACT The role of polymorphonuclear leukocytes (PMN) in protection in the early phase and recovery in the late phase of influenza A virus infection was investigated by the depletion of PMN in, and passive transfer of anti-influenza virus antiserum to, mice with pulmonary infections. The depletion of PMN in normal mice by treatment with monoclonal antibody RB6-8C5 both increased the mortality rate and pulmonary virus titers from the early to the late phase after infection and delayed virus elimination in the late phase. The passive transfer of the antiserum to normal mice before or after infection abolished pulmonary virus propagation in the early phase, during 3 days, or rapidly decreased high virus titers in the plateau phase, on days 3 to 5, as well as accelerated virus elimination in the late phase, on day 7, after infection, respectively. The passive transfer of the antiserum to PMN-depleted mice could neither prevent the more rapid virus propagation in the early phase, diminish the higher virus titers in the plateau phase, nor accelerate the markedly delayed virus elimination in the late phase after infection in comparison to those for controls. The antibody responses to the virus began to increase on day 7 after infection in normal and PMN-depleted mice. The prevention of virus replication, cytotoxic activity in virus-infected cell cultures, and phagocytosis of the virus in vitro by PMN were all augmented in the presence of the antiserum. These results indicate that PMN play an essential role in virus elimination in both protection against and recovery from infection, in cooperation with the antibody response.

Cadherin-related Neuronal Receptors in Incisor Development

2003 ◽  
Vol 82 (1) ◽  
pp. 17-22 ◽  
Author(s):  
E. Fukumoto ◽  
H. Sakai ◽  
S. Fukumoto ◽  
T. Yagi ◽  
O. Takagi ◽  
...  
Keyword(s):  
Early Phase ◽  
Late Phase ◽  
Maturation Stage ◽  
Early Maturation ◽  
Cell Matrix ◽  
Maturation Stages ◽  
Cell Matrix Interactions ◽  
Late Maturation ◽  
Dentin Formation

Cadherins are cell adhesion molecules that are critical for tissue development. In this report, we identified members of the cadherin family cadherin-related neuronal receptors (CNRs) 1 and 5 expressed in rat incisors by the differential display method. Quantitative RT-PCR revealed that CNR1 mRNA is expressed in the secretory stage but reduced in the early-maturation stage, while CNR5 mRNA is expressed in both these stages. In situ hybridization showed that strong expression of CNR1 is strong in the secretory stage, but reduced in the early phase and diminished in the late phase of the early-maturation stage. CNR5 mRNA is expressed almost at the same levels in the secretory and in the early phase of the early-maturation stages but is absent in the late phase of the early-maturation stage. Both CNR1 and 5 mRNA are continuously expressed in odontoblasts. Immunohistology showed that CNR proteins are expressed in the secretory and early-maturation stages of ameloblasts, but no protein expression at the late-maturation stage was observed. CNR proteins were continuously expressed in odontoblasts. We found that recombinant CNR1 binds dental epithelial and mesenchymal cells through N-terminal domain EC1 in vitro. These results suggest that CNR1 and CNR5 may play an important role in enamel and dentin formation, probably through cell-cell and/or cell-matrix interactions.

scholarly journals Tu1607 Mesenchymal Stem Cells Recruitment At the Rectum After Intravenous Injection in the Early Phase but Not Late Phase Inhibited Tumorigenesis in a Rat Model

2013 ◽  
Vol 144 (5) ◽  
pp. S-804
Author(s):  
Takayuki Katsuno ◽  
Masahiro Ochi ◽  
Kazunari Tominaga ◽  
Fumio Tanaka ◽  
Mitsue Sogawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Intravenous Injection ◽  
Rat Model ◽  
Early Phase ◽  
Late Phase

scholarly journals Sterospecific tissue uptake and nuclear accumulation of testosterone in the development of the mouse erythropoietic spleen

Blood ◽  
1976 ◽  
Vol 47 (4) ◽  
pp. 571-580 ◽  
Author(s):  
AJ Hadjian ◽  
JL Spivak ◽  
A Kowarski ◽  
HW Dickerman ◽  
CJ Migeon
Keyword(s):  
Early Phase ◽  
Specific Binding ◽  
Late Phase ◽  
Nuclear Accumulation ◽  
Selective Uptake ◽  
Before And After ◽  
The Media ◽  
Preferential Uptake ◽  
Double Isotope

Abstract A double isotope ratio technique was used to estimate the specific binding of testosterone (T), as opposed to its biologically nonactive stereoisomer, epitestosterone (Epi T). The mouse erythropoietic spleen formed in response to a phenylhydrazine-induced hemolytic anemia was used as the target organ. Spleen minces from preanemic mice, as well as those in the early and late phases of erythropoietic spleen development, were incubated with 10(-9) M of 14C-T and 3H-EpiT, and the selective uptake of T was calculated from the 14C/3H ratio measured in the media before and after incubation, as well as in the subcellular fractions of the minces. Preferential uptake of T was seen in the early phase of development, but not in spleens obtained from preanemic animals or those in the late phase. There was no evidence of metabolic conversion of T or EpiT. The selective uptake of T by early phase spleens was reflected in a preferential nuclear accumulation of T. These data represent the first demonstration of a specific binding of T in vitro to a developing erythroid tissue.

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