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PubMed1981

Ultrastructural study of hemangiomas. 1. Capillary hemangioma of the skin.

The fine structure of capillary hemangiomas from the skin of six young adults was investigated. All the vessels had non-fenestrated endothelial cells. Their intercellular junctions had tight junctions, but desmosome-like structures were also present. Cytoplasmic filaments (50-100A in width) as well as microtubular bodies were present in some of the endothelial cells. The bodies were approximately 0.1 micron in diameter and up to 0.5 micron in length. Subendothelial basement membrane was present and sometimes multilaminated. Pericytes had a feature of endothelial cells, fibroblasts, or smooth muscle cells. "Fibrous long-spacing collagen fibrils" (periodicity: 700-1500A) were seen in the vicinity of pericyte basement membranes or in the intervascular spaces.

Adolescent↗

PubMed1993

Cytotoxic activity of human lymphocytes against differentiated intestinal tumour cell lines.

The natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic activity of human peripheral blood lymphocytes (PBL) against various human tumour cell lines from intestinal origin (WIDR, HT29, Caco-2) has been investigated. The differentiated Caco-2 cells were then used as a model to investigate the cytotoxic activity against enterocyte-like target cells. Caco-2 were seeded on polycarbonate filters and maintained in culture for at least 15 days to allow the differentiation and formation of tight junctions. The integrity of tight junctions was assayed by measuring [3H]mannitol flux from apical to basolateral compartment. Cytotoxic analysis showed that both differentiated and undifferentiated Caco-2 cells were similarly susceptible to NK and LAK activity. The capacity of cytotoxic lymphocytes to kill enterocyte-like cells with intact junctional complex may suggest a direct role of cytotoxic lymphocytes in causing intestinal lesions under inflammatory conditions.

Cell Line↗

PubMed1978

The development of a zonula occludens in peripheral myelin of the chick embryo. A freeze-fracture study.

Sciatic nerves of chick embryos, 12 to 18 days incubation, were examined in freeze-fracture replicas with special emphasis placed on the development of tight junctional contacts in the myelin sheaths. In stages of beginning myelination short isolated particulate chains (focal tight junctions) appear in fracture faces of the adjacent membranes in the outer myelin lamellae, i.e., the outer mesaxon. In stages of progressing myelination these tight junctional elements elongate and become more numerous. They can also be found in the membranes of the inner mesaxons, the paranodal loops and the intramyelinic cytoplasmic inclusions. In fibers of advanced myelinogenesis a fusion of these isolated tight junctions--either end-to-end or at an angle--gives rise to continuous zonulae occludentes. This contact zone extends in the mesaxonal membranes along the direction of the fiber, whereas in paranodal myelin it acquires a helical course joining the membranes of the paranodal loops. It is proposed that this zonula occludens, which seals the cytoplasmic border of the Schwann cell, separates an intramyelinic from an extramyelinic, extracellular space already during the developmental stages of myelinogenesis.

Animals↗

PubMed2000

Interferon beta-1a prevents the effects of lipopolysaccharide on embryonic brain microvessels.

By means of light and electron microscopy we have studied the effect of interferon beta-1a (IFNbeta-1a) in the optic tecta of 20-day-old chick embryos under normal conditions and after exposure to lipopolysaccharide (LPS) which mimics the blood-brain barrier (BBB) disruption in meningoencephalitis. Optic tecta were examined for: (i) ultrastructure by means of transmission electron microscopy; (ii) the immunohistochemical localization of HT7 antigen, a specific marker of differentiation of the brain microvessels; (iii) the brain microvessel permeability, by means of horseradish peroxidase (HRP) tracer; (iv) the expression of microvessel glycoconjugates, by means of lectin histochemistry, using Ricinus communis agglutinin-I (RCA-I), specific for beta-D-galactosyl moieties and Wheat Germ agglutinin (WGA) specific for sialyl and N-acetylglucosaminyl moieties. A morphometric evaluation of brain microvessel permeability and of glycoconjugate expression was also performed. In control- and in IFNbeta-1a-treated embryos, HRP was confined to the vessel lumina which were sealed by the interendothelial tight junctions. RCA-I binding sites were recognizable both in the basal membranes and in the tight junctions, while WGA sites were present on the luminal side of the endothelial cells. HRP was blocked in the vessels lumina by the interendothelial tight junctions. After LPS treatment, HRP showed an extravascular localization and the labeling of microvessels by anti-HT7 antibodies disappeared. RCA-I binding was only found ultrastructurally and appeared as irregularly clustered gold particles, in the cleft of damaged tight junctions, but were no longer detectable in the endothelial basement membranes. After pretreatment of LPS-treated embryos with IFNbeta-1a, the vessel permeability to HRP strongly decreased and the vessels showed the normal pattern of HT7 protein and of the RCA-I binding sites. These results indicate that the changes induced by LPS in the endothelial cells are prevented by IFNbeta-1a.

Animals↗

PubMed1975

A model of NaCl and water flow through paracellular pathways of renal proximal tubules.

To explain how hydrostatic pressure differences between tubule lumen and interstitium modulate isotonic reabsorption rates, we developed a model of NaCl and water flow through paracellular pathways of the proximal tubule. Structural elements of the model are a tight junction membrane, an intercellular channel whose walls transport NaCl actively at a constant rate, and a basement membrane. Equations of change were derived for the channel, boundary conditions were formulated from irreversible thermodynamics, and a pressure-area relationship typical of thin-walled tubing was assumed. The boundary value problem was solved numerically. The principal conclusions are: 1) channel NaCl concentration must remain within a few mOsm of isotonic values for reabsorption rates to be modulated by transtubular pressure differences known to affect this system: 2) basement membrane and channel wall parameters determine reabsorbate tonicity; tight junction parameters affect the sensitivity of reabsorption to transmural pressure; 3) channel NaCl concentration varies inversely with transmural pressure difference; this concentration variation controls NaCl diffusion through the tight junction; 4) modulation of NaCl diffusion through the tight junction controls the rate of isotonic reabsorption; modulation of water flow can increase sensitivity to transmural pressure; 5) no pressure-induced change in permeability of the tight junction or basement membrane is needed for pressure to modulate reabsorption; and 6) system performance is indifferent to the distribution of active transport sites, to the numerical value of the compliance function, and to the relationship between lumen and cell pressures.

Basement Membrane↗

PubMed2006

Study of claudin function by RNA interference.

Claudins are tight junction proteins that play a key selectivity role in the paracellular conductance of ions. Numerous studies of claudin function have been carried out using the overexpression strategy to add new claudin channels to an existing paracellular protein background. Here, we report the systematic knockdown of endogenous claudin gene expression in Madin-Darby canine kidney (MDCK) cells and in LLC-PK1 cells using small interfering RNA against claudins 1-4 and 7. In MDCK cells (showing cation selectivity), claudins 2, 4, and 7 are powerful effectors of paracellular Na+ permeation. Removal of claudin-2 depressed the permeation of Na+ and resulted in the loss of cation selectivity. Loss of claudin-4 or -7 expression elevated the permeation of Na+ and enhanced the proclivity of the tight junction for cations. On the other hand, LLC-PK1 cells express little endogenous claudin-2 and show anion selectivity. In LLC-PK1 cells, claudin-4 and -7 are powerful effectors of paracellular Cl- permeation. Knockdown of claudin-4 or -7 expression depressed the permeation of Cl- and caused the tight junction to lose the anion selectivity. In conclusion, claudin-2 functions as a paracellular channel to Na+ to increase the cation selectivity of the tight junction; claudin-4 and -7 function either as paracellular barriers to Na+ or as paracellular channels to Cl-, depending upon the cellular background, to decrease the cation selectivity of the tight junction.

Animals↗

PubMed1993

Tissue culture of rabbit ciliary body epithelial cells on permeable supports.

The aqueous humor is produced by the epithelium of the ciliary body, a complex structure encircling the anterior segment of the eye. Aqueous humor production occurs by active transport, but the mechanism of this process is not understood. To produce a preparation in which active transport can be investigated, we have attempted to prepare cultures suitable for measurements of ion and water flux. We have grown rabbit ciliary body epithelial cells on permeable supports, coated with several extracellular matrix proteins. We then examined the ability of these proteins to promote the growth of a differentiated layer of epithelial cells. Non-pigmented and pigmented cells formed sheets of contiguous cells when grown on a variety of support media. The most successful substrate was a permeable support produced by Falcon/Becton Dickinson coated with a mixture of collagen IV, laminin and heparan sulfate. Under these conditions, cultures could be maintained for several months, but pigmented cell cultures did not develop a measurable transepithelial resistance (TER), and the TER of non-pigmented cell cultures was typically only 20-30 omega cm2. Much higher TERs exceeding 200 omega cm2 could be measured from non-pigmented cell cultures 3-5 days after plating, but these high values were unstable. Examination of the cultures with electron microscopy revealed that the cells were partially differentiated with the formation of a basal lamina and intercellular junctions. Labelling with a specific monoclonal antibody marker for tight junction protein (ZO-1) suggested that non-pigmented cell cultures showed extensive tight junction formation. The low TER of the non-pigmented cell cultures appears therefore not to be due to the lack of tight junctions but rather to the presence of spaces between cells.

Animals↗

PubMed1990

[Relationship between bronchial reactivity to inhaled acetylcholine, eosinophil infiltration and a widening of the intercellular space in patients with asthma].

The hypothesis that epithelial damage is related to the development of bronchial hyperreactivity has been supported by many studies. Therefore, we further examined whether or not subjects with bronchial epithelium damage showed increased bronchial responsiveness. We took biopsy specimens of the airway mucosa from 20 asthmatic patients with various degrees of disease severity and bronchial hyperreactivity by using a bronchofiber scope. The morphology of the biopsy specimens was studied by electron microscopy. Bronchoscopy was carried out after local anesthesia. Specimens of bronchial mucosa were obtained from 20 asthmatic patients (14 males, 6 females) in remission. The electronmicroscopic studies showed widening of the intercellular space between the epithelial cells and openings of the tight junctions, as well as infiltrations of eosinophils and their granules beneath and between epithelial cells. The tight junction refers to the space between epithelial cells exposed to the airway surface, leading down to the intercellular space. The intercellular space refers to the space between epithelial cells, below the tight junction. Interestingly, eosinophils and their granules were found mainly in the widened intercellular space. The incidence of a widening of the intercellular space was higher in specimens showing eosinophil infiltration than in those not showing eosinophil infiltration. A significant correlation was found between the respiratory threshold to acetylcholine and the percentage of opened tight junctions (r = -0.47, p less than 0.05) and/or the widening of the space between epithelial cells (r = -0.65, p less than 0.01). These results suggest that widening of the intercellular space may be caused by infiltrations of eosinophils and that this widening increases bronchial reactivity.

Acetylcholine↗

PubMed1999

Developmental expression of ZO-1 antigen in the mouse blood-brain barrier.

Tight junction biogenesis during blood-brain barrier development (BBB) in mesencephalon microvessels of mouse embryos of day 9, foetuses of day 15 and 19 and new-born (2-day-old) mice was examined by light and electron microscopy, using monoclonal antibodies recognizing the tight junction peripheral membrane protein ZO-1. A faint spot-like staining began to be recognizable under the light microscope in day 15 vessels in which the endothelial cells showed isolated fusion points between the external plasma membrane leaflets under the electron microscope. A stronger labelling was present in microvessels of day 19 foetuses and new-born animals when the endothelial tight junction appeared completely differentiated. In the immunogold study, gold particles were seen scattered throughout the cytoplasm of endothelial cells of day 15 foetuses. In day 19 foetuses and in the new-born mice, gold particles were located only at the cytoplasmic surfaces of the tight junctions. The results indicate that the ZO-1 protein is a specific molecular marker in the developing brain endothelial tight junctions and that its expression takes place parallel to BBB morphofunctional maturation.

Aging↗

PubMed1974

Osmosis in cortical collecting tubules. ADH-independent osmotic flow rectification.

The present experiments were designed to evaluate the effects of varying the osmolality of luminal solutions on the antidiuretic hormone (ADH)-independent water and solute permeability properties of isolated rabbit cortical collecting tubules. In the absence of ADH, the osmotic water permeability coefficient (cm s(-1)) P(f) (l-->b), computed from volume flows from hypotonic lumen to isotonic bath, was 20 +/- 4 x 10(-4) (SEM); the value of P(f) (b-->l) in the absence of ADH, computed from volume flows from isotonic bath to hypertonic lumen, was 88 +/- 15 x 10(-4) cm s(-1). We also measured apparent urea permeability coefficients (cm s(-1)) from (14)C-urea fluxes from lumen to bath (P(DDurea) (l-->b)) and from bath to lumen (P(DDurea) (b-->l)). For hypotonic luminal solutions and isotonic bathing solutions, P(DDurea) (l-->b) was 0.045 +/- 0.004 x 10(-4) and was unaffected by ADH. The ADH-independent values of P(DDurea) (l-->b) and P(urea) (b-->l) were, respectively, 0.216 +/- 0.022 x 10(-4) cm s(-1) and 0.033 +/- 0.002 x 10(-4) cm s(-1) for isotonic bathing solutions and luminal solutions made hypertonic with urea, i.e., there was an absolute increase in urea permeability and asymmetry of urea fluxes. Significantly, P(DDurea) (l-->b) did not rise when luminal hypertonicity was produced by sucrose; and, bathing fluid hypertonicity did not alter tubular permeability to water or to urea. We interpret these data to indicate that luminal hypertonicity increased the leakiness of tight junctions to water and urea but not sucrose. Since the value of P(f) (b-->l) in the absence of ADH, when tight junctions were open to urea, was approximately half of the value of P(f) (l-->b) in the presence of ADH, when tight junctions were closed to urea, we conclude that tight junctions are negligible paracellular shunts for lumen to bath osmosis with ADH. These findings, together with those in the preceding paper, are discussed in terms of a solubility-diffusion model for water permeation in which ADH increases water solubility in luminal plasma membranes.

Animals↗

PubMedDate not supplied

Influence of retinoic acid on adhesion complexes in human hepatoma cells: a clue to its antiproliferative effects.

Retinoic acid exerts antiproliferative and differentiative effects in normal and transformed in vitro hepatocytes. In order to verify whether these effects are related to a modulation of adhesion molecules, we used Western blot analysis and immunofluorescence microscopy to investigate the E-cadherinl/beta-catenin complex, the main system of adherens junctions, and the occludin/ZO-1 complex present in the tight junctions in HepG2 cells cultured in the presence or absence of retinoic acid. Results showed that retinoic acid treatment increases the amount of beta-catenin bound to E-cadherin by decreasing its tyrosine-phosphorylation level. Similar results were obtained with the tight junction system, in which the amount of occludin/ZO-1 complex is increased by a similar mechanism that reduced the level of ZO-1 phosphorylation on tyrosine. Immunofluorescence images also confirm these results, showing the localization on the cell surface of both adhesion complexes. Their insertion into the plasma membrane could be suggestive of an optimal reassembly and function of adherens and tight junctions in hepatoma cells, indicating that retinoic acid, besides inhibiting cell proliferation, improves cell-cell adhesion, sustaining or inducing the expression of a more differentiated phenotype.

Cadherins↗

PubMed1991

Chloride ion transport in transformed normal and cystic fibrosis epithelial cells.

The inability of beta-adrenergic agonists (eg. isoproterenol) to activate a specific apical membrane chloride channel in epithelial cells is characteristic of cystic fibrosis (CF). The study of these channels has been facilitated by the transformation of human airway epithelial cells. Clonal populations of SV40 large T-antigen transformed airway epithelial cells from both normal and cystic fibrosis individuals have been established. A limitation in the use of these cell lines has been the loss of the ability to form tight junctions after multiple subcultures. In particular, this loss appears to be associated with cell "crisis". A selection protocol that involves growing cells in medium that is high in Ca2+ and supplemented with fetal bovine serum (FBS) has been employed to facilitate progression through crisis. One cell line (1HAEo-) that has a normal phenotype and retains tight junctions post-crisis has been produced using this protocol. Immunofluorescent staining with a monoclonal antibody to the E-cadherin adhesion molecule shows a characteristic pericellular localization, indicating the presence of the junctional complex. The presence of tight junctions has been confirmed by electron microscopy. These cells produce elevated (greater than 30 fold) levels of cAMP in response to exposure to isoproterenol or forskolin. Chloride ion transport, as measured by 36Cl- efflux, is stimulated greater than 2 fold by these agents. Three post-crisis CF cell lines which grow in serum-containing medium have been established. These do not exhibit tight junctions. Elevated (greater than 25 fold) levels of cAMP are detected in these cells after addition of isoproterenol or forskolin, but this increase in cAMP is not accompanied by an increase in 36Cl-efflux. Both normal (1HAEo-) and CF cells show increased 36Cl-efflux following addition of the calcium ionophore A23187. (ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport, Active↗

PubMed1982

Fluorescent membrane probes and the mechanism of maintenance of cellular asymmetry in epithelia.

Individual epithelial cells are asymmetric with respect to morphology, distribution of enzymes, lipid composition, ionic permeability, and sensitivity to drugs and hormones on the apical (mucosal) versus basolateral (serosal) membranes. It has been suggested that the tight junction, which forms the morphological boundary between apical and basolateral surfaces, helps to maintain this cellular asymmetry by forming a barrier to lateral diffusion of membrane constituents across these membranes. We have directly tested this hypothesis by selectively labeling either the apical or basolateral membrane with fluorescent probes and ascertaining 1) whether the probe can diffuse laterally in the membrane, and 2) whether it can pass through the tight junction region to the side of the cell initially not labeled. Our results show that membrane-bound lectins and some lipid probes are incapable of passing through the tight junction region. The lectins are immobile on the cell surface, but the lipid probes diffuse freely in the membrane. We propose that the ability of a lipid probe to pass through the tight junction is correlated with its ability to flip-flop to the inner monolayer of the cell membrane bilayer, and that the tight junction thus forms a barrier to lipids in the outer monolayer only. Differences in diffusion rates of different lipid probes also appear to reflect different physical characteristics of the inner versus outer membrane leaflet.

Animals↗

PubMed2005

Roles of ZO-1, occludin, and actin in oxidant-induced barrier disruption.

Oxidants such as monochloramine (NH(2)Cl) decrease epithelial barrier function by disrupting perijunctional actin and possibly affecting the distribution of tight junctional proteins. These effects can, in theory, disturb cell polarization and affect critical membrane proteins by compromising molecular fence function of the tight junctions. To examine these possibilities, we investigated the actions of NH(2)Cl on the distribution, function, and integrity of barrier-associated membrane, cytoskeletal, and adaptor proteins in human colonic Caco-2 epithelial monolayers. NH(2)Cl causes a time-dependent decrease in both detergent-insoluble and -soluble zonula occludens (ZO)-1 abundance, more rapidly in the former. Decreases in occludin levels in the detergent-insoluble fraction were observed soon after the fall of ZO-1 levels. The actin depolymerizer cytochalasin D resulted in a decreased transepithelial resistance (TER) more quickly than NH(2)Cl but caused a more modest and slower reduction in ZO-1 levels and in occludin redistribution. No changes in the cellular distribution of claudin-1, claudin-5, or ZO-2 were observed after NH(2)Cl. However, in subsequent studies, the immunofluorescent cellular staining pattern of all these proteins was altered by NH(2)Cl. The actin-stabilizing agent phalloidin did not prevent NH(2)Cl-induced decreases in TER or increases of apical to basolateral flux of the paracellular permeability marker mannitol. However, it partially blocked changes in ZO-1 and occludin distribution. Tight junctional fence function was also compromised by NH(2)Cl, observed as a redistribution of the alpha-subunit of basolateral Na(+)-K(+)-ATPase to the apical membrane, an effect not found with the apical membrane protein Na(+)/H(+) exchanger isoform 3. In conclusion, oxidants not only disrupt perijunctional actin but also cause redistribution of tight junctional proteins, resulting in compromised intestinal epithelial barrier and fence function. These effects are likely to contribute to the development of malabsorption and dysfunction associated with mucosal inflammation of the digestive tract.

Actins↗

PubMed2006

Junctional adhesion molecule-a participates in the formation of apico-basal polarity through different domains.

Junctional adhesion molecule (JAM)-A is an integral membrane protein at tight junctions of epithelial cells which associates with the cell polarity protein PAR-3. Here, we demonstrate that downregulation of JAM-A impairs the ability of MDCK II cells to form cysts in a three-dimensional matrix indicating the requirement of JAM-A for the development of apico-basal polarity. To define the regions of JAM-A important for this function, we have generated MDCK II cell lines stably expressing inducible JAM-A mutants. Mutants of JAM-A which were designed to mislocalize strongly impaired the development of cysts and the formation of functional tight junctions. Surprisingly, similar mutants that lacked the PDZ domain-binding motif at the C-terminus were still impaired in apico-basal polarity formation suggesting that additional regions within the cytoplasmic tail of JAM-A are important for the function of JAM-A. A JAM-A mutant lacking the first Ig-like domain necessary for homophilic binding localized to cell-cell contacts similar to wild-type JAM-A. However, despite this same localization, this mutant interfered with cell polarity and tight junction formation. Together our findings suggest an important role for JAM-A in the development of apico-basal polarity in epithelial cells and identify regions in JAM-A which are critical for this role.

Amino Acid Motifs↗

PubMed2002

PI3K signaling is required for prostaglandin-induced mucosal recovery in ischemia-injured porcine ileum.

We have previously shown that PGE(2) and PGI(2) induce recovery of transepithelial resistance (TER) in ischemia-injured porcine ileal mucosa, associated with initial increases in Cl(-) secretion. We believe that the latter generates an osmotic gradient that stimulates resealing of tight junctions. Because of evidence implicating phosphatidylinositol 3-kinase (PI3K) in regulating tight junction assembly, we postulated that this signaling pathway is involved in PG-induced mucosal recovery. Porcine ileum was subjected to 45 min of ischemia, after which TER was monitored for a 180-min recovery period. Endogenous PG production was inhibited with indomethacin (5 microM). PGE(2) (1 microM) and PGI(2) (1 microM) stimulated recovery of TER, which was inhibited by serosal application of the osmotic agent urea (300 mosmol/kgH(2)O). The PI3K inhibitor wortmannin (10 nM) blocked recovery of TER in response to PGs or mucosal urea. Immunofluorescence imaging of recovering epithelium revealed that PGs restored occludin and zonula occludens-1 distribution to interepithelial junctions, and this pattern was disrupted by pretreatment with wortmannin. These experiments suggest that PGs stimulate recovery of paracellular resistance via a mechanism involving transepithelial osmotic gradients and PI3K-dependent restoration of tight junction protein distribution.

16,16-Dimethylprostaglandin E2↗

PubMed2006

Claudin-1 overexpression in melanoma is regulated by PKC and contributes to melanoma cell motility.

Serial analysis of gene expression followed by pathway analysis implicated the tight junction protein claudin-1 (CLDN1) in melanoma progression. Tight junction proteins regulate the paracellular transport of molecules, but staining of a tissue microarray revealed that claudin-1 was overexpressed in melanoma, and aberrantly expressed in the cytoplasm of malignant cells, suggesting a role other than transport. Indeed, melanoma cells in culture demonstrate no tight junction function. It has been shown that protein kinase C (PKC) can affect expression of claudin-1 in rat choroid plexus cells, and we observed a correlation between levels of activated PKC and claudin expression in our melanoma cells. To determine if PKC could affect the expression of CLDN1 in human melanoma, cells lacking endogenous claudin-1 were treated with 200 nM phorbol myristic acid (PMA). PKC activation by PMA caused an increase in CLDN1 transcription in 30 min, and an increase in claudin-1 protein by 12 h. Inhibition of PKC signaling in cells with high claudin-1 expression resulted in decreased claudin-1 expression. CLDN1 appears to contribute to melanoma cell invasion, as transient transfection of melanoma cells with CLDN1 increased metalloproteinase 2 (MMP-2) secretion and activation, and subsequently, motility of melanoma cells as demonstrated by wound-healing assays. Conversely, knockdown of CLDN1 by siRNA resulted in the inhibition of motility, as well as decreases in MMP-2 secretion and activation. These data implicate claudin-1 in melanoma progression.

Blotting, Western↗

PubMed1989

Ultrastructure of Amphiuma distal nephron: evidence for cellular heterogeneity.

To obtain more information on the ultrastructure of the distal nephron of the salamander, Amphiuma, we conducted freeze-fracture electron microscopy and morphometric experiments. In the early distal tubule, the organization of the tight junction is variable, containing from one to two strands in the proximal region and four strands in distal regions. The length density of the tight junction in this segment varies from greater than 60 m/cm2 of apical membrane surface to less than 10/cm2 of apical membrane surface. These observations agree with a previous study demonstrating that the junction of this segment exhibits considerable axial heterogeneity. The junctions of the late distal tubule and collecting tubule are more complex. In the late distal tubule, the tight junction is composed of 6-8 strands, whereas the tight junction of the collecting tubule is composed of 8-12 strands. The collecting tubule contains principal cells and two types of intercalated cells: alpha and beta. The alpha-cells contain a high density of rod-shaped particles in the apical plasma membrane and in membranes of apical cytoplasmic vesicles. The beta-cells contain rod-shaped particles only in the basolateral membrane. In principal cells, we observed a novel organization of intramembranous particles within the apical plasma membrane. A model describing the relationship of the two types of intramembranous particles within the membrane is presented. This study demonstrates that the amphibian and mammalian distal nephron share many morphological characteristics including cellular and axial heterogeneity.

Animals↗