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PubMed2005

Sphingosine 1-phosphate-induced mobilization of intracellular Ca2+ mediates rac activation and adherens junction assembly in endothelial cells.

Sphingosine 1-phosphate (S1P) ligation of endothelial differentiation gene-1 receptor coupled to the heterotrimeric G protein, Gi, promotes endothelial barrier strengthening via Rac-dependent assembly of adherens junctions (AJs). However, the mechanism of Rac activation induced by S1P stimulation remains unclear. In live endothelial cells expressing GFP-Rac, we observed that S1P induced the translocation of Rac to intercellular junctions, resulting in junctional sealing. We investigated the role of intracellular Ca2+ in signaling Rac activation and the enhancement of endothelial barrier function. We observed that S1P activated the release of Ca2+ from endoplasmic reticulum stores, and subsequent Ca2+ entry via lanthanum-sensitive store-operated Ca2+ channels (SOC) after store depletion. Inhibition of Gi, phospholipase C, or inositol trisphosphate receptor prevented the S1P-activated increase in intracellular Ca2+ as well as Rac activation, AJ assembly, and enhancement of endothelial barrier. Chelation of intracellular Ca2+ with BAPTA blocked S1P-induced Rac activation, indicating the requirement for Ca2+ in the response. Inhibition of SOC by lanthanum or transient receptor potential channel 1 (TRPC1), a SOC constituent, by TRPC1 antibody, failed to prevent S1P-induced Rac translocation to junctions and AJ assembly. Thus, our results demonstrate that S1P promotes endothelial junctional integrity by activating the release of endoplasmic reticulum-Ca2+, which induces Rac activation and promotes AJ annealing.

Adherens Junctions↗
PubMed1989

Symplastic Transport of Carboxyfluorescein in Staminal Hairs of Setcreasea purpurea Is Diffusive and Includes Loss to the Vacuole.

The kinetics of symplastic transport in staminal hairs of Setcreasea purpurea was studied. The tip cell of a staminal hair was microinjected with carboxyfluorescein (CF) and the symplastic transport of this CF was videotaped and the digital data analyzed to produce kinetic curves. Using a finite difference equation for diffusion between cells and for loss of dye into the vacuole, kinetic curves were calculated and fitted to the observed data. These curves were matched with data from actual microinjection experiments by adjusting K (the coefficient of intercellular junction diffusion) and L (the coefficient of intracellular loss) until a minimum in the least squares difference between the curves was obtained. (a) Symplastic transport of CF was governed by diffusion through intercellular pores (plasmodesmata) and intracellular loss. Diffusion within the cell cytoplasm was never limiting. (b) Each cell and its plasmodesmata must be considered as its own diffusion system. Therefore, a diffusion coefficient cannot be calculated for an entire chain of cells. (c) The movement through plasmodesmata in either direction was the same since the data are fit by a diffusion equation. (d) Diffusion through the intercellular pores was estimated to be slower than diffusion through similar pores filled with water.

Journal Article↗
PubMed2004

Parametric analysis of intercellular ice propagation during cryosurgery, simulated using monte carlo techniques.

A microscale theoretical model of intracellular ice formation (IIF) in a heterogeneous tissue volume comprising a tumor mass and surrounding normal tissue is presented. Intracellular ice was assumed to form either by intercellular ice propagation or by processes that are not affected by the presence of ice in neighboring cells (e.g., nucleation or mechanical rupture). The effects of cryosurgery on a 2D tissue consisting of 10(4) cells were simulated using a lattice Monte Carlo technique. A parametric analysis was performed to assess the specificity of IIF-related cell damage and to identify criteria for minimization of collateral damage to the healthy tissue peripheral to the tumor. Among the parameters investigated were the rates of interaction-independent IIF and intercellular ice propagation in the tumor and in the normal tissue, as well as the characteristic length scale of thermal gradients in the vicinity of the cryosurgical probe. Model predictions suggest gap junctional intercellular communication as a potential new target for adjuvant therapies complementing the cryosurgical procedure.

Cell Line, Tumor↗
PubMedDate not supplied

Okadaic acid and phorbol esters: comparative effects of these tumor promoters on cell transformation, intercellular communication and differentiation in vitro.

Okadaic acid is a non-12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoter in the mouse skin carcinogenesis system. Here we report on the in vitro activity of okadaic acid in 3 assay systems: BALB/c 3T3 cell transformation, gap junctional intercellular communication (GJIC) in various cell types, and inhibition of induction of differentiation of Friend virus-transformed murine erythroleukemia (MEL) cells. The activity of okadaic acid was compared to that of the phorbol ester tumor promoters TPA and phorbol-12,13-didecanoate (PDD). In a test system involving a 2-week exposure of BALB/c 3T3 cells following 3-methylcholanthrene initiation, okadaic acid at a concentration of 10 ng/ml was equipotent to PDD as a promoter of cell transformation (4.9 and 3.7 foci/dish, respectively). Longer exposures to okadaic acid resulted in cytotoxicity. Okadaic acid-generated as well as PDD-generated transformed foci displayed a selective lack of GJIC between focus cells and surrounding normal cells, i.e., transformed cells communicate among themselves but not with surrounding cells. However, in contrast to TPA, there was no inhibition by okadaic acid, except at toxic doses, of homologous GJIC in BALB/c 3T3 cells or human and mouse keratinocytes. Furthermore, okadaic acid, unlike TPA, did not inhibit MEL cell differentiation. Together, these results indicate that okadaic acid acts as a promoter of cell transformation but that its mechanism of action is different from that of the phorbol ester tumor promoters.

Animals↗
PubMed1998

Physical connections between feeder cells and recipient normal mammary epithelial cells.

Cells of the LA7 rat mammary tumor line stimulate proliferation of normal mouse mammary epithelial cells in culture when in direct physical contact with them. We examined junctional connections between these LA7 feeders and the recipient mouse mammary epithelial cells in order to study the role these junctions may play in growth signaling. Tight junctions and desmosomes between LA7 feeders and mouse mammary cells were detected by immunocytochemistry. These junctions connected every cell of either type with each of its neighbors. Adherens junctions, although evident between mouse mammary cells, could not be detected between LA7 and mouse mammary cells or between LA7 cells themselves. However, E-cadherin, the transmembrane protein of adherens junctions, was present in LA7 cell lysates. beta-catenin, which normally binds cadherins, was detected at the borders of LA7 cells. Presence of gap junctions between LA7 and mouse mammary cells was determined by traverse of lucifer yellow from an injected LA7 cell to surrounding mouse mammary epithelial cells. The experiments thus indicate that three types of intercellular junctions occur between cells active in direct cell-cell-stimulated proliferation signaling.

Animals↗
PubMed1995

Functional expression of gap junction gene Cx43 and the myogenic differentiation of rhabdomyosarcoma cells.

Rhabdomyosarcoma (RD) cells express low levels of the gap junction protein connexin 43 (Cx43), and its mRNA, and display very weak gap junctional intercellular communication (GJIC) as detected by Cx43 immunofluorescence, slot-blot and dye-transfer methods. These cells grow rapidly and show aberrant and incomplete myogenic differentiation. To investigate the role of gap junctions in these cells, the expression of Cx43 with relation to cell growth and myogenic differentiation in RD single-cell subclones-RDL3 and RDL6 is studied. The subclone RDL3 grows slowly and displays better myogenic differentiation. The expression of Cx43, its mRNA and the GJIC in RDL3 is comparable to that in normal myoblasts. Another subclone RDL6 which grows rapidly, but is poorly differentiated, expresses very low levels of Cx43 and its mRNA, and very weak GJIC. By using the calcium phosphate precipitate transfection technique, a full-length cDNA-encoding Cx43 and a pSV2neo have been introduced into the RDL6 cells. Several stably transfected clones have been obtained. A stable Cx43-transfectant clone RDL6/C-4 expresses high level of Cx43 and its mRNA, and results in dramatic increase of GJIC. These cells grow slowly but display the enhanced myogenic differentiation. A correlation between the down-regulation of Cx43 gene expression and a reduced expression of myogenic differentiation in RD cells is is demonstrated. Forced expression of Cx43 not only inhibits cell growth but also correlates with the improved myogenic differentiation of RD cells.

Cell Communication↗
PubMed2003

Regulation of adherens junctions and epithelial paracellular permeability: a novel function for polyamines.

Maintenance of intestinal mucosal epithelial integrity requires polyamines that are involved in the multiple signaling pathways controlling gene expression and different epithelial cell functions. Integrity of the intestinal epithelial barrier depends on a complex of proteins composing different intercellular junctions, including tight junctions, adherens junctions, and desmosomes. E-cadherin is primarily found at the adherens junctions and plays a critical role in cell-cell adhesions that are fundamental to formation of the intestinal epithelial barrier. The current study determined whether polyamines regulate intestinal epithelial barrier function by altering E-cadherin expression. Depletion of cellular polyamines by alpha-difluoromethylornithine (DFMO) reduced intracellular free Ca2+ concentration ([Ca2+]cyt), decreased E-cadherin expression, and increased paracellular permeability in normal intestinal epithelial cells (IEC-6 line). Polyamine depletion did not alter expression of tight junction proteins such as zona occludens (ZO)-1, ZO-2, and junctional adhesion molecule (JAM)-1. Addition of exogenous polyamine spermidine reversed the effects of DFMO on [Ca2+]cyt and E-cadherin expression and restored paracellular permeability to near normal. Elevation of [Ca2+]cyt by the Ca2+ ionophore ionomycin increased E-cadherin expression in polyamine-deficient cells. In contrast, reduction of [Ca2+]cyt by polyamine depletion or removal of extracellular Ca2+ not only inhibited expression of E-cadherin mRNA but also decreased the half-life of E-cadherin protein. These results indicate that polyamines regulate intestinal epithelial paracellular barrier function by altering E-cadherin expression and that polyamines are essential for E-cadherin expression at least partially through [Ca2+]cyt.

Adherens Junctions↗
PubMed2001

[Studies of intercellular communication in human rhabdomyosarcoma cell lines of different metastatic potential].

OBJECTIVE: To investigate the relationship between intercellular communication and three human rhabdomyosarcoma (RMS) cell lines of different metastatic potential. METHODS: Indirect immunofluorescent staining and laser scanning confocal microscope (ISCM) were used to detect connexin 43 (CX43), a molecule related with gap junctional intercellular communication (GJIC). Fluorescence redistribution after photobleaching (FRAP) was used to detect function of GJIC. RESULTS: A high level of CX43 protein expression was revealed in normal human myoblasts. CX43 protein was mainly localized on the surface of cells and sometimes in cytoplasm. CX43 expression was decreased in RMS cells. Both the detection rates and fluorescent intensity of CX43 decreased when the metastatic potential of RMS increased (P < 0.05). In contrast to normal, the fluorescence recovery rates of the RMS cells decreased and there was a negative correlation between the function of GJIC and malignancy of RMS cell lines (P < 0.05). CONCLUSION: Varying degrees of GJIC inhibition may correlate with different metastatic potential of RMS. This may help to determine the malignant behavior of RMS and be used as a prognostic index of RMS.

Animals↗
PubMed1997

Endocytosis of horseradish peroxidase by brain microvascular and umbilical vein endothelial cells in culture: an ultrastructural and morphometric study.

The ability to form tight junctions and the paucity of fluid phase endocytosis showed by brain microvacular endothelial cells (BMECs) make up the structural basis of the blood-brain barrier (BBB). Most studies on cultured BMECs focused on intercellular junctions, whereas endocytosis received lesser attention. We studied endocytosis of horseradish peroxidase in primary and passage 1 and 2 BMEC cultures from rat brain as well as in human umbilical vein endothelial cell (HUVEC) culture. Endocytic activity was also analyzed in passage 1 BMECs treated with lipopolysaccharide (LPS, 1 microg/ml for 4 h), which mimics BBB disruption in bacterial meningoencephalitis. The percent of cytoplasmic area occupied by endocytic profiles (vesicles <70 nm and vacuoles >70 nm) and their mean number per cell were significantly lower in primary and passaged BMEC than in HUVEC cultures. The area and number of endocytic profiles significantly increased in BMECs after exposure to LPS. BMECs cultured under standard conditions may be a suitable model for studying the mechanism of increased fluid phase endocytosis in certain diseases and injury states.

Animals↗
PubMed2003

Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA.

Helicobacter pylori translocates the protein CagA into gastric epithelial cells and has been linked to peptic ulcer disease and gastric carcinoma. We show that injected CagA associates with the epithelial tight-junction scaffolding protein ZO-1 and the transmembrane protein junctional adhesion molecule, causing an ectopic assembly of tight-junction components at sites of bacterial attachment, and altering the composition and function of the apical-junctional complex. Long-term CagA delivery to polarized epithelia caused a disruption of the epithelial barrier function and dysplastic alterations in epithelial cell morphology. CagA appears to target H. pylori to host cell intercellular junctions and to disrupt junction-mediated functions.

Animals↗
PubMed1996

Cloning and characterization of a new armadillo family member, p0071, associated with the junctional plaque: evidence for a subfamily of closely related proteins.

Cell contacts of the adherens type are organized around transmembrane proteins of the cadherin family. Whereas the extracellular domains mediate homophilic interactions between cadherins of neighbouring cells the cytoplasmic domains organize a set of proteins into the junctional plaque. Among these junctional plaque proteins are members of the armadillo gene family, beta-catenin, plakoglobin (gamma-catenin), B6P/plakophilin and p120. These proteins are assumed to play a key role in cell cell signalling through intercellular junctions. Here we report cloning of a cDNA encoding a new armadillo family member, p0071, closely related to p120 and B6P/plakophilin and more distantly related to armadillo, plakoglobin, beta-catenin and other members of the gene family. The deduced amino acid sequence encodes a basic protein of 1,211 amino acids with a central armadillo repeat region which is conserved in sequence and organization of its ten individual motifs between p120, B6P/plakophilin and p0071. In contrast the end domains of the three proteins are variable in size and sequence. The RNA coding for p0071 is expressed in all tissues examined. Using antibodies generated against the armadillo repeat region of the protein we show that p0071 is localized at cell-cell borders and is expressed in the desmosomal plaque of some cultured epithelial cells. The protein seems to be an accessory component of the desmosomal plaque as well as of other adhesion plaques and might be involved in regulating junctional plaque organization and cadherin function. Our data provide evidence for a subfamily of armadillo related proteins that share not only structural features but also have in common their localisation in the junctional plaque. We therefore suggest that family members exert similar functions and might be involved in cell signalling through cell contacts.

Amino Acid Sequence↗
PubMed2000

Reduced levels of connexin43 in cervical dysplasia: inducible expression in a cervical carcinoma cell line decreases neoplastic potential with implications for tumor progression.

Loss of gap junctional intercellular communication (GJIC) has been linked to aberrant proliferation and an enhanced neoplastic phenotype. Many human tumors, including the cervical carcinoma line HeLa, have been reported to be deficient in expression of the gap junction protein connexin43 (Cx43) and GJIC. To determine if this is an early event in carcinogenesis, we utilized immunohistochemistry to screen a series of cervical biopsy samples and demonstrated a major reduction in Cx43 expression in dysplastic regions compared to normal epithelia. To determine whether this loss influences the neoplastic behavior of cervical carcinoma cells, we have constructed HeLa cell lines in which Cx43 expression can be induced in response to doxycycline. This approach allows for the discrimination of Cx43-mediated effects from those due to pre-existing clonal heterogeneity. Cx43 induction in these cells led to assembly of functional junctions but did not alter growth control in vitro as measured by logarithmic growth, saturation density or focus formation when in co-culture with growth-controlled fibroblasts. However, Cx43 induction decreased two indices of neoplasia: it reduced anchorage-independent growth and attenuated the growth rate of tumor xenografts. These results indicate that established HeLa cell lines are unresponsive to Cx43-mediated signals which are thought to mediate growth control of non-transformed cells, however, Cx43 expression can still reduce aspects of the neoplastic phenotype of these cells, indicating that loss of connexin signaling in dysplastic cells may contribute to their neoplastic progression.

Animals↗
PubMed2001

The postsynaptic spectrin/4.1 membrane protein "accumulation machine".

An important aspect of the function of the membrane-associated cytoskeleton has been suggested to be to trap and retain selected transmembrane proteins at points on the cell surface specified by cell adhesion molecules. In the process, cell adhesion molecules are cross-linked to each other, and so junctional complexes are strengthened. In this short review, we will discuss recent advances in understanding the role of this "accumulation machine" in postsynaptic structures. Function in the brain depends on correct ordering of synaptic intercellular junctions, and in particular the recruitment of receptors and other apparatus of the signalling system to postsynaptic membranes. Spectrin has long been known to be a component of postsynaptic densities, and recent advances in molecular cloning indicate that beta spectrins at PSDs are all "long" C-terminal isoforms characterised by pleckstrin homology domains. Isoforms of protein 4.1 are also present at synapses. All four 4.1 proteins are represented in PSD preparations, but it is 4.1R that is most enriched in PSDs. 4.1R binds to several proteins enriched in PSDs, including the characteristic PSD intermediate filament, alpha-internexin. Both 4.1 and spectrin interact with ionotropic glutamate receptors (AMPA and NMDA receptors, respectively): 4.1 stabilises AMPA receptors on the cell surface. By linking these receptors to the cytoskeletal and cell adhesion molecules that specify glutamatergic synapses, the membrane protein accumulation machine is suggested to direct the formation of postsynaptic signalling complexes.

Animals↗
PubMedDate not supplied

Connexin 33: a rodent-specific member of the gap junction protein family?

Gap junctional intercellular communication between Sertoli cells and between Sertoli cells and spermatogonia is considered to play a key role in the regulation of both proliferation and differentiation of germ cells. A member of the gap junction protein family, Connexin 33 (cx33), probably has an inhibitory effect on the formation of gap junctions and so far it is the only cx that has been exclusively found in rat and mouse testes. Thus, this connexin seems to be a special member of the cx family. Using immunohistochemistry, Western blot analysis, polymerase chain reaction, and reverse transcription (RT)-PCR (tissue homogenate and microdissected cells), we studied the possible occurrence of cx33 at the protein, the DNA, and the RNA level in human testis. Whereas immunohistochemistry using the only commercially available anti-cx33 antibody showed similar labeling to the rat within the seminiferous epithelium, we could not find any further evidence for the existence of cx33 using Western blot analysis, PCR, and RT-PCR in human testis. Based on the demonstration of the staining pattern of mitochondria in human germ cells and on preabsorption studies, we could demonstrate anti-cx33 antibody cross-reacting with mitochondrial ferritin, a protein localized in the mitochondria of human testicular spermatids. Therefore, we were not able to abide by the suspicion that cx33 is present in human testis. Additionally, it was not possible to demonstrate cx33 via PCR and immunohistochemistry in the testis of different mammals (dog, cattle, pig, horse, and marmoset monkey) with normal spermatogenesis. These data indicate that cx33 seems to be the first rodent-specific testicular cx.

Amino Acid Sequence↗
PubMed2001

Induction of a bystander effect in HeLa cells by using a bigenic vector carrying viral thymidine kinase and connexin32 genes.

We previously showed that gap junction intercellular communication mediates the bystander effect in anticancer gene therapy with the herpes simplex virus thymidine kinase (HSV-tk) and ganciclovir. Because most cancer cell lines have lost their ability to communicate through gap junctions, we investigated whether we could induce such a communication by transferring a gene for a gap junction. We transfected a vector carrying the HSV-tk (tk) and gap junction (connexin (Cx) 32) genes (Cx32(+)tk(+)) into noncommunicating HeLa cells. We compared the cytotoxicity of ganciclovir with mixtures of these cells and HeLa cells that expressed (Cx32(+)) or did not express (Cx32(-)) the Cx32 gene. The bystander effect was strong when the two mixed cell types expressed Cx32 (i.e., Cx32(+)tk(+) cells and Cx32(+)tk(-) cells). Only 25% of cells survived in this communicating mixture, even when only 10% of the cells were Cx32(+)tk(+). There was also a moderate bystander effect when the Cx32(+)tk(+) cells were mixed with noncommunicating HeLa cells in a 50% ratio. These results demonstrated that the bystander effect is enhanced by Cx32 and suggested that expression of Cx in only one cell type in a mixture can cause a bystander effect. Mol. Carcinog. 30:176--180, 2001.

Bleomycin↗
PubMed1995

Changes in gap junction permeability, gap junction number, and connexin43 expression in lindane-treated rat liver epithelial cells.

The pesticide lindane (gamma-hexachlorocyclohexane) is a mammalian neurotoxin and hepatocarcinogen. Lindane can inhibit gap junctional intercellular communication (GJIC) and this effect may contribute to its toxic properties. The mechanism of inhibition of GJIC by lindane in WB-F344 rat liver epithelial cells was studied to determine if altered gap junction permeability, gap junction number, and/or gap junction protein (connexin43) expression were involved. GJIC was monitored by fluorescent Lucifer Yellow CH dye microinjection (dye-coupling). Gap junction number was quantified visually after indirect immunostaining of gap junctions using an anti-connexin43 monoclonal antibody. Connexin43 mRNA and protein levels were determined by Northern and Western blotting, respectively. Short-term treatment (10-30 min) with lindane (50 microM) resulted in the rapid (within 10 min), nearly complete loss of dye-coupling but no changes in gap junction number of connexin43 mRNA or protein levels. Medium-term treatment (1-4 hr) resulted in the loss of dye-coupling, gap junctions, and phosphorylated connexin43 proteins. Long-term treatment (1-14 days) led to reductions in dye-coupling, total connexin43 protein, and connexin43 mRNA. Nuclear run-on assays indicated that transcription of the connexin43 gene was reduced nonspecifically by lindane. These data indicate that reductions in gap junction permeability, number, and expression may be involved in the inhibition of GJIC depending on pesticide treatment duration.

Animals↗
PubMed2006

Cancer gene therapy: combination with radiation therapy and the role of bystander cell killing in the anti-tumor effect.

Current anti-cancer modalities such as surgery, chemo- and radiation therapies have only limited success in cancer treatment. Gene therapy is a promising new tool to improve outcomes. In this review, first we summarize the various strategies to kill tumor cells, and then focus on the bystander effect of gene therapy. A variety of strategies, such as gene-directed enzyme pro-drug therapy, activation of an anti-tumor immune attack, application of replication-competent and oncolytic viral vectors, tumor-specific as well as radiation- and hypoxiainduced gene expression, might be applied to target tumor cells. We put special emphasis on the combination of these approaches with local tumor irradiation. Using the available vector systems, only a small portion of cancer cells contains the therapeutic genes under clinical situations. However, cells directly targeted by gene therapy will transfer death signals to neighboring cancer cells. This bystander cell killing improves the efficiency of cancer gene therapy. Death signals are delivered by cell-to-cell communication through gap junction intercellular contacts, release of toxic metabolites into the neighborhood or to larger distances, phagocytosis of apoptotic bodies, and the activation of the immune system. Bystander cell killing can be enhanced by the introduction of gap junction proteins into cells, by further activating the immune system with immune-stimulatory molecules, or by introducing genes that help the transfer of cytotoxic genes and/or metabolites into bystander cells. In conclusion, although bystander cell killing can improve therapeutic effects, there should be additional developments in cancer gene therapy for a more efficient clinical application.

Animals↗
PubMed2005

Divergent roles for glutathione in lindane-induced acute and delayed-onset inhibition of rat myometrial gap junctions.

Previous studies have shown that the insecticide lindane (gamma-hexachlorocyclohexane) induces a biphasic inhibition of gap junction intercellular communication that is accompanied by oxidative stress. The present study investigates the hypothesis that depletion of cellular glutathione (GSH) is a mechanistic link between lindane-induced oxidative stress and inhibition of myometrial gap junctions. Exposure to 100 or 200 microM lindane rapidly (within 1 min) increased myometrial cell generation of superoxide, as measured by superoxide dismutase-inhibitable cytochrome c reduction, and superoxide production remained elevated for up to 60 min of exposure. To measure gap junction communication, Lucifer yellow dye was injected into myometrial cells, and dye transfer to adjoining cells was monitored. Cells were exposed to lindane with or without GSH modulators, and dye transfer was determined at the end of a 1-h exposure to 100 microM lindane (acute phase) and 24 h after termination of lindane exposure (secondary phase). The acute phase of lindane-induced inhibition of dye transfer was prevented by GSH depletion with L-buthionine-[S,R]-sulfoximine (BSO) and enhanced by GSH augmentation with GSH monoethyl ester or L-2-oxothiazolidine-4-carboxylate (OTC). In contrast, the secondary, delayed-onset phase of lindane-induced inhibition of dye transfer was enhanced by GSH depletion with BSO and prevented by GSH augmentation with GSH monoethyl ester or OTC. Changes in cellular GSH by the pharmacological modulators were confirmed by high performance liquid chromatography. These results suggest that GSH is required in the acute phase but protects against the secondary phase of lindane-induced inhibition of myometrial gap junctions.

Animals↗