Role of tight-junctional pathways in bile salt-induced increases in colonic permeability

1983 ◽  
Vol 245 (6) ◽  
pp. G816-G823 ◽  
Author(s):  
R. W. Freel ◽  
M. Hatch ◽  
D. L. Earnest ◽  
A. M. Goldner

The effects of a dihydroxy bile salt, taurochenodeoxycholate (TCDC), on the permeability and conductance of isolated, short-circuited segments of the rabbit descending colon were examined using conventional Ussing chamber techniques. Increasing concentrations of TCDC (1℃4 mM) produced dose-dependent increases in sodium backflux (JNas leads to m) and tissue conductance (Gt) when applied to either the mucosal or serosal salines. However, mucosal addition was twice as potent in increasing JNas leads to m and Gt at 4 mM. Tracer experiments indicated that the transepithelial serosal-to-mucosal fluxes of sodium and mannitol are via an aqueous, unrestricted, free-solution pathway, while albumin movements are restricted through this pathway both in the absence and presence of mucosal TCDC. The changes in JNas leads to m, JMans leads to m, and Gt caused by 4 mM mucosal TCDC were largely reversed by rinsing the mucosal chamber with fresh buffer. It was also observed that osmotically induced volume flows in the serosal-to-mucosal direction could offset or reverse the changes in Gt produced by 2 mM mucosal TCDC, suggesting that the enhanced conductance pathway is in series with the lateral intercellular spaces. Taken together, these results suggest that low concentrations of TCDC alter the integrity of tight-junctional complexes between the epithelial cells of the rabbit colon.

1981 ◽  
Vol 241 (6) ◽  
pp. G469-G477 ◽  
Author(s):  
P. R. Kvietys ◽  
J. M. McLendon ◽  
D. N. Granger

In an autoperfused dog ileum preparation, artificial pressure, venous outflow pressure, blood flow, and arteriovenous oxygen difference were measured while bile and bile salt solutions, at physiological concentrations, were placed in the lumen. Intraluminal placement of endogenous bile, synthetic bile, or bile salt solutions increased ileal blood flow (99 +/- 10, 94 +/- 20, and 104 +/- 17%, respectively) and oxygen uptake (30 +/- 5, 36 +/- 9, and 28 +/- 5%, respectively). Endogenous bile pretreated with cholestyramine, a bile salt-sequestering resin, did not alter ileal blood flow, yet increased ileal oxygen uptake by 11 +/- 3%, a response similar to that observed while Tyrode's solution (the vehicle) was in the lumen. Intra-arterial infusion of bile salts increased ileal blood flow in a dose-dependent manner, while not significantly altering ileal oxygen uptake. The results of the present study indicate that bile salts play an important role in the functional (postprandial) hyperemia in the ileum by 1) directly dilating the ileal vasculature and 2) enhancing ileal metabolism during their active absorption.


1970 ◽  
Vol 48 (1) ◽  
pp. 39-NP ◽  
Author(s):  
N. T. DAVIES ◽  
K. A. MUNDAY ◽  
B. J. PARSONS

SUMMARY Fluid transfer by isolated everted sacs of rat jejunum, ileum and intact colon prepared from adrenalectomized-nephrectomized rats 48 h after operation was reduced when compared with that of sacs prepared from untreated controls (P < 0·001). Angiotensin at 10−10 g/ml significantly (P < 0·01) stimulated fluid transfer by intestinal sacs prepared from the adrenalectomized-nephrectomized rats; all three regions of gut were equally sensitive. Fluid transfer was similarly reduced in stripped colon sacs prepared from adrenalectomized-nephrectomized rats. Angiotensin had a dose-dependent biphasic action on fluid transfer by stripped colon sacs: low concentrations (10−11 and 10−12 g/ml) stimulated (P < 0·05), whilst high concentrations (10−9 and 10−8 g/ml) inhibited fluid transfer (P < 0·01). Histological examination of the colon preparations showed that the stripping procedure removed the ganglia, indicating that both angiotensin effects were due to direct action on the colon mucosa. The significance of these results is discussed in relation to the role of angiotensin in the control of salt and fluid transport by the mammalian kidney and other epithelial tissues.


1980 ◽  
Vol 188 (2) ◽  
pp. 321-327 ◽  
Author(s):  
D Billington ◽  
C E Evans ◽  
P P Godfrey ◽  
R Coleman

The conjugated trihydroxy bile salts glycocholate and taurocholate removed approx. 20–30% of the plasma-membrane enzymes 5′-nucleotidase, alkaline phosphatase and alkaline phosphodiesterase I from isolated hepatocytes before the onset of lysis, as judged by release of the cytosolic enzyme lactate dehydrogenase. The conjugated dihydroxy bile salt glycodeoxycholate similarly removed 10–20% of the 5′-nucleotidase and alkaline phosphatase activities, but not alkaline phosphodiesterase activity; this bile salt caused lysis of hepatocytes at approx. 10-fold lower concentrations (1.5–2.0mM) than either glycocholate or taurocholate (12–16mM). At low concentrations (7 mM), glycocholate released these enzymes in a predominantly particulate form, whereas at higher concentrations (15 mM) glycocholate further released these components in a predominantly ‘soluble’ form. Inclusion of 1% (w/v) bovine serum albumin in the incubations had a small protective effect on the release of enzymes from hepatocytes by glycodeoxycholate, but not by glycocholate. These observations are discussed in relation to the possible role of bile salts in the origin of some biliary proteins.


2008 ◽  
Vol 60 (1) ◽  
pp. 11-23 ◽  
Author(s):  
Zanka Bojic-Trbojevic ◽  
Milica Bozic ◽  
Ljiljana Vicovac

The effects of steroids on galectin-1 (gal-1) were studied in HTR-8/SVneo cells by immunocytochemistry, cell-based ELISA, the MTT proliferation test and the Matrigel TM invasion test. Dexamethasone (DEX), progesterone (PRG), and mifepristone (RU486) were used. Gal-1 was modulated in a steroid- and dose-dependent manner by DEX, which mildly but significantly stimulated production at low concentrations (0.1-10 nM), and inhibited it at 100 nM, while the effects of PRG and RU486 were opposite. HTR-8/SVneo cell invasion of Matrigel was significantly decreased in the presence of DEX and lactose. The obtained data support the proposed regulatory role of steroids in trophoblast gal-1 production.


2016 ◽  
Vol 9 (4) ◽  
pp. 565-575 ◽  
Author(s):  
A. Dawidziuk ◽  
G. Koczyk ◽  
D. Popiel

The ability of fungal plant pathogens to exude bioactive compounds is an important element of competition in a changing environment. The filamentous fungi usually retain a number of adaptations related not only to the production of toxic compounds by themselves but also to the mitigation of exogenous influences by toxins present in the environment. We examined a distinct effect of toxins on morphology, growth patterns and gene expression after stimulation in mycotoxin-producing and nonproducing isolates representing four evolutionarily divergent species (and chemotypes) within the Fusarium genus (Fusarium graminearum, Fusarium oxysporum, Fusarium proliferatum and Fusarium verticillioides). The aim of our work was to investigate the influence of mycotoxins present in the environment on fungal isolates belonging to evolutionarily divergent complexes within Fusarium genus. The results point to retention of resistance mechanisms in non-producer isolates (F. oxysporum) and specific dose-dependent differences in response to other mycotoxins. In particular, the growth of Fusarium graminearum (confirmed zearalenone and trichothecene producer) was shown to be significantly inhibited by fumonisin B1 and deoxynivalenol. Conversely, spread of Fusarium verticillioides was accelerated by low concentrations (0.5 mg/l) of nivalenol and zearalenone and deoxynivalenol addition resulted in upregulation of the fumonisin poliketyde synthase (FUM1). The basics of competition between divergent fusaria can be described by ‘rock-paper-scissors’ theory, but some of the effects can be explained by other interactions, e.g. autotoxicity of deoxynivalenol and the potential role of low doses of trichothecenes and zearalenone acting as a ‘warning signal’ for competing species.


1988 ◽  
Vol 65 (3) ◽  
pp. 1274-1280 ◽  
Author(s):  
F. J. al-Bazzaz ◽  
J. Veech ◽  
D. Arenberg

Variations in the volume and width of lateral intercellular spaces (LICS) of dog tracheal mucosa in vitro were investigated by use of stereological and linear measurements of electron micrographs. Alterations in the volume or width of LICS were then correlated with physiological conditions and electrical parameters. LICS were quite narrow between the ciliated cells compared with those around the nonciliated dark cells (goblet, brush, and basal cells). LICS comprised 6.8 +/- 2.9% of tissue volume in preparations that were mounted in an Ussing chamber and short-circuited, whereas in unmounted and open-circuited tissues it occupied only 1 +/- 0.2% of the volume of the preparations (P less than 0.016, n = 5). The effects of stimulation of Cl secretion by 1 microM epinephrine were tested. In seven epinephrine-treated tissues LICS volume was 2.9 +/- 0.9% of total epithelial volume compared with 8.7 +/- 2.9% in control tissues (P less than 0.015). The width of LICS around dark cells in epinephrine-treated tissues was 0.42 +/- 0.06 micron compared with 0.98 +/- 0.13 micron in control tissues (P less than 0.001). The data suggest that LICS act as pliable fluid reservoirs that empty and collapse on stimulation of Cl secretion.


Development ◽  
1979 ◽  
Vol 54 (1) ◽  
pp. 75-98
Author(s):  
Michael Solursh ◽  
Marilyn Fisher ◽  
Stephen Meier ◽  
Carl T. Singley

The development of the sclerotome is considered as a model for the formation of mesenchyme from an epithelium. In early epithelial somites, transmission and scanning electron microscopy indicate considerable ultrastructural similarity between the future sclerotome and dermamyotomal regions. Subsequently, these two regions diverge in their development. In the forming dermamyotome, junctional complexes become more extensive and the cells become elongated, closely applied to each other, and have angular surface contours. In the forming sclerotome, there is an early reduction in apical junctions. The cells elongate, keeping their original polarity, and acquire numerous filopodia which contain punctate junctions at sites of cell-to-cell contact. Associated with cellular extension is an expansion of the intercellular spaces which do not contain any ultrastructurally recognizable material. Evidence for a role of hyaluronic acid in the expansion of the intercellular spaces is presented. As identified by the susceptibility of cetylpyridinium chloride precipitates to Streptomyces hyaluronidase and chromatographic separation of chondroitinase ABC digestion products, as much as 64–68% of the [3H]glucosamine-labeled glycosaminoglycans synthesized by explanted somites is hyaluronic acid. In addition, hyaluronidase-sensitive label is localized in the intercellular spaces of the sclerotome, as demonstrated by autoradiography. When ,Streptomyces hyaluronidase is injected in ovo into living embryos, the sclerotomal mesenchyme differentiates morphologically, but intercellular spaces are drastically reduced. It is hypothesized that the sclerotomal cells produce a hyaluronate-enriched extracellular matrix which is inflated by hydration to mediate the expansion of the sclerotomal mass towards the notochord.


1975 ◽  
Vol 66 (4) ◽  
pp. 445-471 ◽  
Author(s):  
J A Schafer ◽  
C S Patlak ◽  
T E Andreoli

We studied salt and water absorption in isolated rabbit superficial proximal straight tubules perfused and bathed with solutions providing oppositely directed transepithelial anion gradients similar to those which might obtain in vivo. The perfusing solution contained 138.6 mM Cl- 3.8 mM HCO-3 (pH 6.6) while the bathing solution contained 113.6 mM Cl- and 25 mM HCO-3 (pH 7.4); the system was bubbled with 95% O2-5% CO2. At 37 degrees C, net volume absorption (Jv nl min-1 mm-1) was 0.32 +/- 0.03 (SEM); Ve, the transepithelial voltage (millivolts; lumen to bath), was +3.1 +/- 0.2. At 21 degrees C, Ve rose to +3.7 +/- 0.1 and Jv fell to 0.13 +/- 0.01 (significantly different from zero at P less than 0.001); in the presence of 10(-4)M ouabain at 37 degrees C, Ve rose to +3.8 +/- 0.1 and Jv fell to 0.16 +/- 0.01 (P less than 0.001 with respect to zero). In paired experiments, the ouabain- and temperature-insensitive moieties of Jv and Ve became zero when transepithelial anion concentration gradients were abolished. Titrametric determinations net chloride flux at 21 degrees C or at 37 degrees C with 10(-4) M ouabain showed that chloride was the sole anion in an isotonic absorbate. And, combined electrical and tracer flux data indicated that the tubular epithelium was approximately 18 times more permeable to Cl- than to HCO-3. We interpret these results to indicate that, in these tubules, NaCl absorption depends in part on transepithelial anion concentration gradients similar to those generated in vivo and in vitro by active Na+ absorption associated with absorption to anions other than chloride. A quantitative analysis of passive solute and solvent flows in lateral intercellular spaces indicated that fluid absorption occurred across junctional complexes when the osmolality of the lateral intercellular spaces was equal to or slightly less than that of the perfusing and bathing solutions; the driving force for volume flow under these conditions depended on the fact that sigmaHCO3 exceeded sigmaCl.


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