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PubMed1991

Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions.

Attenuated Vibrio cholerae vaccine strains specifically mutated in genes encoding cholera toxin (CT) are still capable of causing mild to moderate diarrhea. Culture supernatants of V. cholerae strains, both CT-positive and CT-negative, were examined in Ussing chambers, and a toxin was found that increases the permeability of the small intestinal mucosa by affecting the structure of the intercellular tight junction, or zonula occludens. The activity of this toxin is reversible, heat-labile, sensitive to protease digestion, and found in culture supernatant fractions containing molecules between 10 and 30 kDa in size. Production of this factor (named ZOT for zonula occludens toxin) correlates with diarrheagenicity of V. cholerae strains in volunteers and may represent another virulence factor of infectious diarrhea that must be eliminated to achieve a safe and effective live oral vaccine against cholera.

Animals↗
PubMed1984

Partitioning of paracellular conductance along the ileal crypt-villus axis: a hypothesis based on structural analysis with detailed consideration of tight junction structure-function relationships.

Current models of intestinal transport suggest cells which absorb ions are located on the villus while secretory cells are located in the crypt and putatively have paracellular pathways which are highly conductive to Na+. One approach to assess possible variation in small intestinal paracellular conductance along the crypt-villus axis is to morphometrically analyze the structural aspects of crypt and villus tight junctions (TJs) which relate to paracellular resistance. Such detailed analysis of junctional structure in this heterogeneous epithelium would permit one to compare intestinal TJ structure-function relationships with those in a structurally simpler epithelium such as that of toad urinary bladder. This comparison would also be of considerable interest since previous similar comparisons have failed to consider in detail the geometric dissimilarity between these two epithelia. We applied light, electron microscopic, and freeze-fracture morphometric techniques to guinea pig ileal mucosa to quantitatively assess, for both crypts and villi, linear TJ density, relative surface contributions, and TJ strand counts. Mean linear TJ densities were 76.8 m/cm2 for crypt cells and 21.8 m/cm2 for villus absorptive cells. Mean TJ strand counts were 4.45 for undifferentiated crypt cell TJs and 6.03 for villus absorptive cell TJs. The villus constituted 87% and the crypt 13% of total surface. We utilized these data to predict paracellular conductance of crypts vs. villi based on equations derived from those of Claude (P. Claude, J. Membrane Biol. 39:219-232, 1978). Such analysis predicts that 73% of ileal paracellular conductance is attributable to the crypt. Furthermore, we obtained literature values for paracellular resistance in mammalian ileum and toad urinary bladder and for toad bladder TJ structure and linear density and constructed a relationship which would allow us to more accurately compare TJ structure-function correlates between these two epithelia. Such a comparison, which considers both surface amplification and TJ structure and distribution in these epithelia, shows that one would predict in vitro measured values for paracellular resistance should be approximately two orders of magnitude less in mammalian ileum than in toad urinary bladder. This predicted discrepancy (115-fold) correlates well with the observed difference (100-fold).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2006

Development of an in vitro blood-brain barrier model to study the effects of endosulfan on the permeability of tight junctions and a comparative study of the cytotoxic effects of endosulfan on rat and human glial and neuronal cell cultures.

Endosulfan, an organochlorine (OC) insecticide that belongs to the cyclodiene group, is one of the most commonly used pesticides to control pests in vegetables, cotton, and fruits. Porcine brain microvascular endothelial cells were used to develop a model to study the effects of endosulfan on the permeability of tight junctions in the blood-brain barrier (BBB). BBB permeability, measured as transendothelial electrical resistance, decreased in a dose- and time-dependent manner when treated with alpha-endosulfan, beta-endosulfan, or endosulfan sulfate. Cytotoxicity testing revealed that the three endosulfans did not cause cell death at concentrations of 10 microM and below. The ratio of the average permeability of the filter-grown endothelial cell monolayer to 14C-endosulfan (Pe) going from the outer to the inner compartments with that going from the inner to the outer compartments was approximately 1:1.2-2.1 after exposure to concentrations of 0.01-10 microM. alpha-Endosulfan, beta-endosulfan, and endosulfan sulfate had cytotoxic effects on rat glial (C6) and neuronal (PC12) cell cultures as well as on human glial (CCF-STTG1) and neuronal (NT2) cell cultures. The effects of alpha-endosulfan were highly selective, with a wide range of LC50 values found in the different cultures, ranging from 11.2 microM for CCF-STTG1 cells to 48.0 microM for PC12 cells. In contrast, selective neurotoxicity was not so manifest in glial and neuronal cell cultures after exposure to endosulfan sulfate, as LC50 values were in the range of 10.4-21.6 microM. CCF-STTG1 cells were more sensitive to alpha-endosulfan and endosulfan sulfate, whereas NT2 cells were more sensitive to beta-endosulfan.

Animals↗
PubMed1999

Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis.

BACKGROUND & AIMS: Mechanisms of diarrhea in ulcerative colitis (UC) are still unknown. Functional and structural characterization of epithelial barrier and transport properties in ulcerative colitis (UC) was performed. METHODS: Inflamed sigmoid colon epithelium from UC patients was studied by alternating current impedance analysis to determine the pure epithelial resistance as a measure of intestinal barrier function. Tight junction (TJ) structure was investigated by freeze-fracture electron microscopy. RESULTS: Although total wall resistance was reduced in UC by 50%, impedance analysis uncovered a much more pronounced barrier defect. Epithelial resistance decreased from 95 +/- 5 to 20 +/- 3 omega3. cm2, which in conventional analysis is masked by an increase in subepithelial resistance from 14 +/- 1 to 36 +/- 3 omega3. cm2 caused by inflammation. This was paralleled by a change in epithelial cell TJ structure in UC. Strand count decreased from 6.94 +/- 0.25 to 4.76 +/- 0.47 at the surface and from 7.26 +/- 0.31 to 5.46 +/- 0.37 in the crypts. CONCLUSIONS: The inflamed colonic mucosa in UC has an impaired barrier function that is much more pronounced than previously assumed. An altered TJ structure contributes to this barrier defect which, because of increased back leak, can reduce net ion transport. Thus, a leak-flux mechanism contributes to the diarrhea in UC.

Chloride Channels↗
PubMed1993

Sodium caprate elicits dilatations in human intestinal tight junctions and enhances drug absorption by the paracellular route.

The effects of the absorption enhancer sodium caprate on human intestinal epithelial cells were investigated using Caco-2 cell monolayers. The effects on epithelial integrity and drug transport are dependent on time and concentration and are decreased by Ca2+, most likely through the formation of Ca2+ soaps. Morphological data indicate that exposure to sodium caprate results in cytoskeletal changes and in structural alterations of the tight junctions in the form of dilatations, while the effects on the apical cell membranes are limited. We conclude that sodium caprate increases the absorption of drugs mainly by the paracellular route.

Calcium↗
PubMed2006

Differences in expression patterns of the tight junction proteins,claudin 1, 3, 4 and 5, in human ovarian surface epithelium as compared to epithelia in inclusion cysts and epithelial ovarian tumours.

Human ovarian surface epithelium (OSE), regarded as the precursor cell of epithelial ovarian adenocarcinoma, is not a fully developed epithelium when situated on the ovarian surface. It lacks epithelial characteristics such as the cell-cell adhesion factor epithelial (E)-cadherin, but as we have shown earlier, this OSE can form functional tight junctions (TJs) in culture. Recent gene-expression data on ovarian adenocarcinoma has pointed out a family of TJ proteins, the claudins, to be highly expressed in malignant compared to benign ovarian tumours. The purpose of this study was to investigate the distribution of claudin 1-5 proteins in cultured OSE (n=4), normal ovarian (n=11), benign (n=8), borderline (n=7) and ovarian cancer (n=22) tissues. We found that a weak or absence of expression of claudin 3 and claudin 4 in surface OSE changed to typical cell-border localisation in OSE of inclusion cysts in the normal ovarian stroma. Semiquantitative estimations of immunoblots showed that claudin 3 was significantly increased in ovarian adenocarcinomas compared to benign and borderline-type tumours. Claudin 4 was significantly increased in both borderline-type and ovarian adenocarcinomas compared to benign tumours, whereas no changes were found for claudin 1 or 5. Concerning relation to Federation for International Gynaecology and Obstetrics (FIGO) grade, claudin 3, but not claudin 4, was significantly increased in moderately, poorly and undifferentiated adenocarcinomas compared to well-differentiated and borderline-type tumours. No significant changes were noticed for any claudin with regard to FIGO stages. We conclude that both claudin 3 and 4, even though they differ in expression during ovarian malignant transformation, might be used as novel markers for ovarian tumours. The observations of lack of claudin 4 and low expression of claudin 3 in OSE strengthen our current knowledge about the biological nature of these cells as an undeveloped epithelium.

Adenocarcinoma↗
PubMed1989

Oestradiol 17 beta-glucuronide increases tight-junctional permeability in rat liver.

By using rat liver perfusion under one-pass conditions with a single pulse of horseradish peroxidase (HRP), the biliary output of HRP was used as an indicator of paracellular permeability change caused by the cholestatic compound oestradiol 17 beta-glucuronide (E17G). Since E17G reduced bile flow, we have also used, during the assessment of junctional permeability after E17G treatment, the choleretic compound taurodehydrocholate to enhance bile flow back to control levels. At both low and restored bile flow rates, the acute administration of E17G (3.4 mumol) increased the HRP peak height, thereby indicating that one of the hepatotoxic actions of E17G is to increase the permeability of hepatic tight junctions. The action of E17G in affecting bile acid secretion and biliary volume are also explored.

Animals↗
PubMed1995

Starch microspheres induce pulsatile delivery of drugs and peptides across the epithelial barrier by reversible separation of the tight junctions.

Non-parenteral administration of peptide drugs is prevented by the limited permeability of the epithelia lining the mucosal tissues. As a new approach to non-parenteral delivery, degradable starch microspheres (dsm) were coated with insulin and administered to the mucosal side of monolayers of human intestinal epithelial (Caco-2) cells in vitro. The microspheres induced a pulsed delivery of insulin across the epithelium that lasted for 1-2 h. The pulsed delivery correlated with a reversible appearance of focal dilatations in the tight junctions between the epithelial cells, indicating that dsm enhance the delivery of insulin by the paracellular route. These results provide an explanation for the previously observed absorption enhancing properties of dsm.

Analysis of Variance↗
PubMed1975

Complex tight junctions of epithelial and of endothelial cells in early foetal brain.

?The morphology of epithelial and of endothelial intercellular junctions in human foetal (9-15 weeks gestation) and sheep foetal (50, 60 and 125 days gestation, term 147 days) brain has been studied using the freeze-fracture technique and thin section transmission electronmicroscopy. Freeze-fracture replicas of the choroid plexus of both early human and sheep foetuses showed that the choroidal ependymal cells are linked at the ventricular surface by tight junctions. Freeze-fracture replicas of foetal cortical endothelial cell junctions showed that they are still more complex than those of choroidal epithelial cells, in all specimens so far examined. In some 60 day sheep foetuses the dye Alcian blue, which binds to plasma albumin and which iselectrondense when treated with osmium tetroxide, was injected intravenously a few minutes prior to fixation. The dye penetrated from blood into brain extracellular space and c.s.f. but apparently not by an intercellular route. The dye was found in a tubular system (endoplasmic reticulum) in both choroidal epithelial and cortical endothelial cells. The possibility that protein penetrates into the foetal brain and c.s.f. by a transcellular route is discussed. The possible significance of these findings in relation to previous ideas and studies of the development of blood-brain barrier mechanisms is also considered.

Animals↗
PubMed2006

Evaluation of tight junction protein 1 encoding zona occludens 1 as a candidate gene for albuminuria in a Mexican American population.

Albuminuria, a hallmark of diabetic nephropathy, has been shown to be significantly heritable in multiple studies. Therefore, the identification of genes that affect susceptibility to albuminuria may lead to novel avenues of intervention. Current evidence suggests that the podocyte and slit diaphragm play a key role in controlling the selective sieve of the glomerular filtration barrier, and podocyte-specific genes have been identified that are necessary for maintaining its integrity. We therefore investigated the role of gene variants of tight junction protein (TJP1) which encodes another slit diaphragm-associated protein zona occludens 1 as risk factors for albuminuria in the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), which consists of extended Mexican-American families with a high prevalence of type 2 diabetes. Albuminuria, defined as an albumin (mg/dl) to creatinine (mg/dl) ratio (ACR) of 0.03, which is approximately equivalent to a urinary albumin excretion (UAE) >30 mg/day, was present in a total of 14.9% of participants, and 31% had type 2 diabetes. The TJP1 exons, flanking intronic sequence, and putative proximal promoter regions were investigated in this population. Twentynine polymorphisms, including 7 nonsynonymous SNPs, were identified and genotyped in all subjects of this study for association analysis. Three sets of correlated SNPs, which include 3 exonic SNPs, were nominally associated with ACR (p value range 0.007-0.049); however, the association with the discrete trait albuminuria was not significant (p value range 0.094-0.338). We conclude that these variants in TJP1 do not appear to be major determinants for albuminuria in the SAFDGS; however, they may play a minor role in its severity in this Mexican-American population. Further examination of the TJP1 gene region in this and other cohorts will be useful to determine whether ZO-1 plays a significant role in glomerular permselectivity.

Adolescent↗
PubMed1995

Confluent monolayers of bile duct epithelial cells with tight junctions.

The culture of fully differentiated intrahepatic bile duct epithelial cells (IBDECs) to use as a model for the in vivo intrahepatic biliary tract has not been established. IBDECs from normal rat livers were grown on a collagen-coated permeable filter and formed a confluent monolayer 7 days after being plated. Positive reactions for cytokeratin-19 and retained gamma-glutamyl transpeptidase (GGTP) activity were shown. The transepithelial electrical resistance between the apical and the basolateral compartment culture chambers increased with the culture age and plateaued after the 7th day. The resulting cultured cells displayed a number of characteristics. (1) The cells formed a thin, continuous monolayer and displayed microvilli on the apical surface and junctional complexes between the cells, consistent with in vivo IBDECs. (2) Cells cultured for more than 7 days prevented the passage of horseradish peroxidase (HRP) and ruthenium red through paracellular pathways. (3) Seven-day-old cultures displayed a mean transepithelial electrical resistance of 137.3 omega-cm2, which decreased by 27.1% from its initial level after cell treatment with ethylenediamineteraacetic acid (EDTA). These results indicate that confluent IBDEC monolayers are well differentiated and polarized with tight junctions (TJs) between the cells. These cell monolayers can provide a useful and relevant model for the in vitro study of various in vivo bile duct phenomena.

Animals↗
PubMed1986

Effects of tumor promoters on LLC-PK1 renal epithelial tight junctions and transepithelial fluxes.

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) irreversibly dissipates the electrical potential difference (PD) across LLC-PK1 renal epithelial cell sheets in a dose-dependent manner. The promoter is equally effective when presented to either cell surface. TPA is also equally effective at dissipating the apical-negative PD or the heretofore undescribed apical-positive PD, both of which can exist spontaneously across this monolayer. Diffusion potentials arising from imposed NaCl gradients across LLC-PK1 cell sheets are likewise reduced by TPA. The non-tumor-promoting parent compound, phorbol, is ineffective, but the more hydrophilic TPA analogue, phorbol 12,13-dibutyrate (PDBU) is as effective as TPA. Unlike TPA, the effects of PDBU are reversible. By observing the (paracellular) fluxes of D-mannitol and polyethylene glycol, these effects on PD are shown to be due to increased permeability of the tight junctions. This effect is immediately reversible once PDBU is removed. These findings are discussed in light of the ramifications of the breakdown of epithelial compartments in vivo and the role this could play in the regulation of epithelial cell growth.

Carcinogens↗
PubMed1994

Evidence that growth hormone stimulates milk synthesis by direct action on the mammary gland and that prolactin exerts effects on milk secretion by maintenance of mammary deoxyribonucleic acid content and tight junction status.

Both PRL and GH play a role in maintaining lactation in the rat, although GH can only maintain pup weight gain at around 50% of the control value, whereas PRL can maintain weight gain close to 90% in the absence of GH. In this study we examined the effects of PRL and GH deficiency (using bromocriptine and an antiserum to rat GH) on milk yield and composition in lactating rats. Treatment with bromocriptine to suppress PRL secretion for 48 h led to a 57% decrease in milk yield with a concomitant decrease in milk protein and lactose yields, but no decrease in fat output. This led to the production of milk with a lower lactose concentration but increased concentrations of protein and particularly fat (increased 100%), which suggests that GH serves an auxiliary role by maintaining an energy-rich milk for the neonate when PRL secretion is reduced. This decrease in milk synthesis was accompanied by decreases in total mammary DNA content and increased milk sodium concentrations. The latter indicates the opening of tight junctions between mammary epithelial cells, which normally occurs during dedifferentiation and involution of the mammary gland. This suggests that PRL maintains milk synthesis at least in part by inhibiting epithelial cell loss and maintaining cellular differentiation. A deficiency in GH, by contrast, caused only a small decrease (24%) in milk yield and had no effect on the major constituents of milk or on milk sodium concentrations or total mammary DNA content. When animals were made deficient in both PRL and GH, however, there was a further marked decrease (88%) in milk volume along with the yields of all major milk constituents, confirming our previous findings that PRL and GH are the major regulators of milk synthesis. Recent studies have indicated that GH exerts direct effects on mammary gland growth, but its actions on milk secretion have been proposed to be mediated indirectly via insulin-like growth factor-I (IGF-I). We, therefore, inhibited lactation by inducing PRL and GH deficiency for 48 h and then attempted to reinitiate it by administering GH either systemically or by local oil-based implants into the mammary gland. Oil-based GH implants were as effective in stimulating milk secretion in the treated (but not contralateral, control) gland as was systemic GH treatment. Thus, GH does act directly on the mammary gland to stimulate milk synthesis, although this does not rule out the possibility that GH acts by stimulating local production of IGF-I.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Chloride conductance of frog skin: localization to the tight junctions?

The pathway(s) of passive conductive Cl transport across isolated frog skin are analyzed by electrophysiological techniques including microelectrode impalement of principal cells. It is found that the apical membrane of granular cells is virtually impermeable for Cl. Substitution of mucosal Cl by anions except NO3 and SCN decreases Cl-related tissue conductance (gCl) with first order kinetics. NO3 and SCN block gCl with half-maximal concentration of 18 and 5 mM, respectively. Omission of serosal Cl has little effect on gCl unless the inhibiting anions NO3 or SCN are used. The putative Cl channel blocker diphenylaminocarbonic acid (DPC) and some analogs inhibit gCl, half-inhibitory concentration of the most potent dichloro-DPC is 10(-6) M. The inhibitors act only from the mucosal side. Slow dissipation of gCl after abolition of Na entry across the apical membranes which can be prevented by preceding blockage of the Na-K-ATPase with ouabain suggests that the intracellular Na activity might influence the permeability of the Cl pathway. It is supposed that this control involves microfilaments between the cytoskeleton and the tight junctions with Cl-specific permeation sites in outer regions of the junctional complex.

Amiloride↗
PubMed1995

Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro.

The intracellular signaling involved in the mechanism of action of zonula occludens toxin (ZOT) was studied using several in vitro and ex vivo models. ZOT showed a selective effect among various cell lines tested, suggesting that it may interact with a specific receptor, whose surface expression on various cells differs. When tested in IEC6 cell monolayers, ZOT-containing supernatants induced a redistribution of the F-actin cytoskeleton. Similar results were obtained with rabbit ileal mucosa, where the reorganization of F-actin paralleled the increase in tissue permeability. In endothelial cells, the cytoskeletal rearrangement involved a decrease of the soluble G-actin pool (-27%) and a reciprocal increase in the filamentous F-actin pool (+22%). This actin polymerization was time- and dose-dependent, and was reversible. Pretreatment with a specific protein kinase C inhibitor, CGP41251, completely abolished the ZOT effects on both tissue permeability and actin polymerization. In IEC6 cells ZOT induced a peak increment of the PKC-alpha isoform after 3 min incubation. Taken together, these results suggest that ZOT activates a complex intracellular cascade of events that regulate tight junction permeability, probably mimicking the effect of physiologic modulator(s) of epithelial barrier function.

Actins↗
PubMed1989

Bovine brain endothelial cells express tight junctions and monoamine oxidase activity in long-term culture.

The passage of substances across the blood-brain barrier is regulated by cerebral capillaries which possess certain distinctly different morphological and enzymatic properties compared to capillaries of other organs. Investigations of the functional characteristics of brain capillaries have been facilitated by the use of cultured brain endothelial cells, but in most studies a number of characteristics of the in vivo system are lost. To provide an in vitro system for studies of brain capillary functions, we developed a method of isolating and producing a large number of bovine brain capillary endothelial cells. These cells, absolutely free of pericyte contamination, are subcultured, at the split ratio of 1:20 (20-fold increase of the cultured surface), with no apparent changes in cell morphology up to the fiftieth generation (10 passages). Retention of endothelial-specific characteristics (factor VIII-related antigen, angiotensin-converting enzyme, and nonthrombogenic surface) is shown for brain capillary-derived endothelial cells up to passage 10, even after frozen storage at passage 3. Furthermore, we showed that bovine brain capillary endothelial cells retain, up to the fiftieth generation, some of the characteristics of the blood-brain barrier: occurrence of tight junctions, paucity of pinocytotic vesicles, and monoamine oxidase activity.

Animals↗
PubMedDate not supplied

Increased Ca++ or mg++ concentration reduces relative tight-junction permeability to Na+ in the cortical thick ascending limb of Henle's loop of rabbit kidney.

We have tested whether increased Ca++ and Mg++ concentrations have an effect on transepithelial voltage (PDte) and transepithelial resistance (Rte) in isolated perfused cortical thick ascending limbs (cTAL) of rabbit kidney. The divalent cations added at 2.5, 5.0 and 10.0 mmol.l-1 to the lumen or peritubular bath perfusate led to a concentration-dependent increase in Rte. The maximal response in Rte was observed between 5 and 10 mmol.l-1. No significant change in active transepithelial potential difference (PDte) was observed. The increase in Rte still occurred when the transcellular current was reduced by Ba++ (3 mmol.l-1) added to the lumen perfusate. This suggests that the increase in Rte caused by Ca++ and Mg++ is due to a modification of the paracellular shunt pathway. In the absence of active transport, i.e. when furosemide (5.10(-5) mol.l-1) was added to the lumen perfusate. Ca++ and Mg++ reduced the transepithelial diffusion potential generated by a NaCl gradient established across the epithelium, and thus produced a reduction of the relative permeability for Na+ over Cl- (PNa+/PCl-) of the paracellular shunt pathway. This indicates that divalent cations increase Rte by reducing the sodium permeability of the tight junctions. The observed Ca++ and Mg++ induced reduction of the sodium permeability of the paracellular pathway corresponds to a decrease in net Na+ reabsorption by 5-10%. Since it has been demonstrated that peptide hormones such as parathyrin (PTH) modulate divalent cation and NaCl reabsorptions, in a second series of experiments we tested the effects of PTH (2-20 USP.l-1) and dbcAMP (10(-3) mol.l-1) on PDte and Rte of isolated perfused cTAL segments of rabbit nephron. Neither Rte nor PDte were affected by PTH or dbcAMP.

Animals↗
PubMed1983

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

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.

Animals↗