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M Manfait

Publications and source records attributed to M Manfait.

At least 55 records · Page 3Linked to original sources
PubMed1998

Pirarubicin nuclear uptake does not correlate with its induced cell death effect during reversal of multidrug resistance by quinine in human K562 and CEM leukemic cells.

A number of small and lipophilic cations are able to reverse in vitro the resistance to anthracyclines and other natural products through their interaction with P-glycoprotein or P-gp. However, some modulators do not interact with P-gp. We have demonstrated in a previous a work, using confocal laser microspectrofluorometry, that quinine does not increase nuclear anthracycline uptake in multidrug-resistant Chinese hamster ovary LR73 cells. In this case the LR73 cells were transfected with the mdr1 gene. Moreover, quinine induced in these cells an increase of mdr1 gene expression. In the present study, we investigated verapamil and quinine for their ability to increase nuclear pirarubicin uptake in multidrug-resistant K562R and CEMR human leukemic cell lines. These two cell lines resist, respectively, to doxorubicin and vinblastine and both overexpress the P-gp. Verapamil was able to restore nuclear pirarubicin in both cell lines. On the other hand, quinine was unable to significantly increase nuclear pirarubicin uptake. Both modulators were able to restore pirarubicin sensitivity in both resistant cell lines. After treatment with quinine, mdr1 gene and P-gp expression was not significantly altered as observed previously in the LR73 cells. This suggest that the effect of quinine on mdr1 gene expression is dependent on the cell line studied. These data suggest that quinine could modify the molecular environment of anthracyclines and/or its binding to a possible cytoplasmic target, and that the mechanisms by which anthracyclines induce cell death, and ways by which chemotherapy fails in multidrug-resistant leukemic cells remain complex and are related to more than one target.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Neutrophil elastase promotes rapid exocytosis in human airway gland cells by producing cytosolic Ca2+ oscillations.

The molecular and ionic mechanisms responsible for the regulation of mucus exocytosis in human airway gland cells remain poorly defined. To determine whether dynamic changes of intracellular free Ca2+ concentration [Ca2+]i can promote different exocytotic responses, we monitored dynamic changes in [Ca2+]i and secretory granule (SG) exocytosis in individual human tracheal submucosal serous gland (HTG) cells. These changes were in response to exposure of the cells to three different secretagogues associated with airway inflammation and disease: human neutrophil elastase (HNE), histamine, and ATP. Dynamic changes in [Ca2+]i from single cells were determined with Indo-1/AM using quantitative UV laser microspectrofluorometry. The rate of SG exocytosis was measured in single cells by fluorescence videomicroscopy of SG degranulation and by the ELISA method. Exposure of HTG cells to a low concentration of HNE (1.0 microM) caused a high rate of SG exocytosis (52% decrease in the initial quinacrine fluorescence) during the first 8-min stimulation period compared with that observed following exposure of the cells to 100 microM histamine (10% decrease) or 100 microM ATP (6% decrease). In contrast to a rapid and transient rise in [Ca2+]i induced by histamine (1.0-100 microM) and ATP (10-100 microM), HNE (0.01-1 microM) generated asynchronous oscillations in [Ca2+]i over the first 8-min period. Depletion of internal Ca2+ stores with thapsigargin (500 nM) induced a significant reduction (P < 0.01) in the observed increases in [Ca2+]i upon addition of each of the secretagogues, but did not greatly affect the SG exocytotic responses. Interestingly, the removal of extracellular Ca2+ (+5 mM EGTA) significantly reduced (P < 0.01) both the [Ca2+]i increases and the rate of SG exocytosis following exposure to the secretagogues. We also demonstrate that the influx of extracellular Ca2+ and [Ca2+]i oscillations rather than the absolute level of [Ca2+]i regulate the rapid onset and extent of exocytotic responses to HNE in airway gland cells. Taken together, these results provide strong evidence that [Ca2+]i is a critical intracellular messenger in the regulation of exocytosis process in human airway gland cells.

Adenosine Triphosphatases↗
PubMed1998

Confocal scanning microspectrofluorometry reveals specific anthracyline accumulation in cytoplasmic organelles of multidrug-resistant cancer cells.

We used confocal microspectrofluorometry to investigate intracellular distribution of pirarubicin or THP-DOX in parental K562, CEM, and LR73 tumor cells and their corresponding multidrug-resistant (MDR) strains. Each spectrum of a recorded image was considered as a combination of cell autofluorescence and fluorescence of the drug. In the cytoplasm of parental K562, CEM, and LR73 cells, THP-DOX fluorescence emission profile was similar to that of free drug in aqueous buffer. The (I550nm/I600nm) ratio was 0. 50 +/- 0.1. However, in the cytoplasm of resistant cells the 550-nm band profile was modified. The I550nm/I600nm ratio was 0.85 +/- 0.2 in MDR K562 cells, which is significantly different from the ratio in sensitive cells (p<0.01). This appeared first to correspond to accumulation and self-oligomerization of THP-DOX in cytoplasmic organelles of MDR cells. Transfection of LR73 cells with the mdr1 gene conferred this characteristic on the resistant LR73R cells. Bodipy-ceramide, a trans-Golgi probe, was co-localized with the typical fluorescence emission peak at 550 nm observed in the cytoplasm of MDR cells. This organelle has been shown to be more acidic in MDR cells. Moreover, this specific pattern was similar to that observed when anthracycline is complexed with sphingomyelin. The typical fluorescence emission peak at 550 nm decreased in MDR cells incubated simultaneously in the presence of the drug and quinine, verapamil, or S9788. Growth inhibitory effect and nuclear accumulation of THP-DOX data obtained on LR73R and LR73D cell lines showed that only during reversion of resistance by verapamil and S9788 was an increase of nuclear THP-DOX accumulation observed. Our data suggest that characteristics of molecular environment, such as higher pH gradient or lipid structures, would be potential mechanisms of multidrug-resistance via the sequestration of anthracyclines.

Animals↗
PubMed1998

Uptake and intracellular distribution of 4-aminofluorescin-labelled poly(L-lysine citramide imide) in K562 cells.

4-Aminofluorescein (F1-NH2) was conjugated with various macromolecular carriers of the poly(L-lysine citramide)-type which were hydrophobised by ethyl (C2), heptyl (C7), and dodecyl (C12) alkyl groups attached to the pendent carboxyl of the lysine moieties present in repeating units. The dye was used to label the carriers and monitor their intracellular fate after introduction within the incubation medium of K562 cells. The labelled hydrophobised carriers formed multimolecular compacted aggregates stabilised by the balance of attractive hydrophobic interactions and repulsive electrostatic forces in the aqueous culture medium. The apparent molecular weights and the sizes of these aggregates were determined by Size Exclusion Chromatography (SEC) and by light scattering respectively. Comparison was made of the cell distribution of free and conjugated F1-NH2 in the cell cytoplasm and nucleus by using fluorescence microscopy and laser microspectrofluorometry. It was shown that cell uptakes resulted from adsorptive pinocytosis and depended on hydrophobicity and aggregation of the conjugates. The influence of physical entrapment of free-F1-NH2 within the hydrophobic microdomains formed by aggregates F1-NH2 conjugates was also discussed.

Chromatography, Gel↗
PubMed1998

Role of the vacuolar H+-ATPase in daunorubicin distribution in etoposide-resistant MCF7 cells overexpressing the multidrug-resistance associated protein.

Some multidrug-resistant cell lines efflux anticancer drugs but do not overexpress the well-known P-glycoprotein pump or Pgp. A 190 kDa or multidrug-resistant associated protein (MRP) has been identified and described as an MDR mediator. Many studies on cells overexpressing MRP and Pgp, show a concentration of the drug inside cytoplasmic vesicles followed by an exocytotic process. We studied daunorubicin (DNR) subcellular distribution in the presence of an H+-ATPase pump inhibitor 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD) and verapamil (VPL) in two human breast adenocarcinoma MCF7 etoposide-resistant and adriamycin-resistant cell lines, overexpressing respectively MRP (MCF7/VP) and Pgp (MCF7/ADR). Nucleo-cytoplasmic distribution of daunorubicin was carried out using scanning confocal microspectrofluorometry. This technique allows the determination of nuclear accumulation of anthracyclines. Our results show that NBD was able to increase the nuclear accumulation of DNR in MCF7/VP but not in MCF7/ADR cells. Similarly, NBD could reverse DNR resistance in MCF7/VP cells but had no effect on DNR cytotoxicity in MCF7/ADR cells. VPL caused a significant increase in nuclear accumulation of DNR in MCF7/VP and MCF7/ADR cells. Incubation of MCF7/VP and MCF7/ADR cells with VPL, increased the sensitivity of these cells. These data demonstrate clearly that even if vesicular sequestration can happen in cells overexpressing MRP and Pgp proteins, only the MRP protein is able to extrude the drug through intracellular vesicles and efflux. In cells overexpressing Pgp, drug efflux probably takes place directly at the membrane level.

4-Chloro-7-nitrobenzofurazan↗
PubMed1998

FT-IR spectroscopy as an emerging method for rapid characterization of microorganisms.

Statistical methods such as principal component analysis and cluster analysis were used to analyze ATR-FT-IR spectra obtained from bacterial whole cells. Both methods gave satisfactory results and are conclusive in showing that they can discriminate and classify bacterial strains of clinical origin exhibiting different resistance mechanisms. This approach places FT-IR spectroscopy at the forefront of those new potential techniques that could be used in the rapid screening of microorganisms.

Escherichia coli↗
PubMed1997

Evidence for reversal of multidrug resistance by quinine in LR73 cells without alteration of nuclear pirarubicin uptake and down-regulation of mdr1 gene expression.

Confocal laser microspectrofluorometry was used to investigate restoration of nuclear pirarubicin (THP-DOX) accumulation and sensitivity by verapamil, quinine and S9788 in 2 variants of the Chinese hamster ovary cell lines LR73, selected for resistance to doxorubicin (LR73D) or transfected with the mdr1 gene (LR73R). The 2 resistant cell lines present a multidrug-resistance phenotype (MDR). Verapamil and S9788, which interact with P-glycoprotein (P-gp), were able to restore nuclear THP-DOX accumulation in LR73R and LR73D cells to a level equivalent to that in sensitive cells. On the other hand, quinine was unable to increase nuclear THP-DOX accumulation significantly even at a concentration of 50 microM. All modulators completely restored THP-DOX sensitivity in resistant cell lines. Our results also show that verapamil and S9788 allow high nuclear drug accumulation, whereas quinine did not affect nuclear accumulation. The effect of quinine on the mdr1 gene expression was determined by the use of reverse transcription coupled with polymerase chain reaction. After a 2 hr treatment with 20 microM of quinine, mdr1 gene expression increased slightly.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

ATR-FTIR spectroscopic investigation of E. coli transconjugants beta-lactams-resistance phenotype.

Hyphenation of attenuated total reflection Fourier transform infrared spectroscopy and cluster analysis has been used to characterise a susceptible Escherichia coli K12 strain and the transconjugants TEM-1, TEM-2, TEM-3, SHV-2, SHV-3, SHV-4. A good discrimination of the susceptible strain from the transconjugants was obtained. Although a limited success was achieved in the differentiation of SHV and TEM phenotypes in general, results obtained with TEM-2 and SHV-3 were convincing. Spectral differences observed are ascribed to the global effects of the conjugation process, particularly their repercussions in the nucleic acids and carbohydrate absorbing regions, rather than to beta-lactamase point-mutations.

Conjugation, Genetic↗
PubMed1997

Structure-activity relation in camptothecin antitumor drugs: why a detailed molecular characterisation of their lactone and carboxylate forms by Raman and SERS spectroscopies?

Lactone and carboxylate forms of potent antitumor agents, camptothecins (CPTs) have been studied by Raman, Fourier-transform Raman (FT-Raman) and surface-enhanced Raman scattering (SERS) spectroscopy. Similarity of the Raman spectra of CPTs with corresponding FT-Raman spectra in the near-infrared allowed the latter to be compared with their SERS counterparts in order to analyse the interaction of the drugs with silver colloids. Different types of silver colloids (reduced with sodium borohydride or sodium citrate, with or without activation by anions) have been evaluated. Citrate-reduced colloid, activated with chloride anions (CAS) has been found to be the best compromise for SERS studies of both forms of CPTs. We suggest that in general CPTs are adsorbed on CAS via the nitrogen in ring B and are more inclined to a flat orientation than to a perpendicular one. However, probable interactions of substitution groups and/or of the COO- groups of hydrolysed CPTs with the CAS surface introduce some particularities in the adsorption patterns. As a result, SERS spectra are highly sensitive to hydrolysis and substitutions at distant rings of CPT and uniquely characteristic of each of the CPT derivatives. The pronounced hydrolysis-induced changes, similar in the Raman and SERS spectra of CPTs, involve similar vibrations in the spectra of different CPTs. Vibrational assignments, proposed for the main Raman and SERS bands of CPT and its derivatives (21-lactam-S-CPT, 10,11-(methylenedioxy)-CPT, CPT-11, SN-38 and topotecan) indicate that most of the bands which decreased upon lactone hydrolysis are those preferentially related to stretching modes of the quinoline rings A and B, and the bands which increased are those of the ring D stretching modes. Our data make the spectroscopic approach very promising for the further investigations of the molecular mechanisms of biological activity of CPTs.

Antineoplastic Agents↗
PubMed1997

ATR-FTIR spectroscopic investigation of imipenem-susceptible and -resistant Pseudomonas aeruginosa isogenic strains.

The primary mechanism of imipenem resistance in Pseudomonas aeruginosa has been ascribed to an outer membrane impermeability owing to a loss of expression of protein D2. Attenuated total reflection-Fourier transform infrared spectroscopy in conjunction with statistical methods has been used as a new approach to rapidly discriminate four isogenic strains of P. aeruginosa--susceptible, less susceptible, and highly resistant to imipenem-- and to follow the structural modifications related to this low permeability. Decomposition of the broad protein and carbohydrate contours into underlying Gaussians and comparison of the susceptible and highly resistant strain provided quantitative and ultrastructural information on these strains. This methodology allows for discrimination not of the mutation itself but of its consequences observed in the protein and carbohydrate absorption regions. Its association with other existing biochemical methods may be envisaged since it may allow for rapid orientation of investigations in the field of bacterial resistance diagnosis.

Bacterial Outer Membrane Proteins↗
PubMed1997

Anthracycline subcellular distribution in human leukemic cells by microspectrofluorometry: factors contributing to drug-induced cell death and reversal of multidrug resistance.

There is a large discrepancy between the changes in drug accumulation and the changes in drug cytotoxicity that accompany development of anthracycline in multidrug-resistant cells. Moreover, although different molecular targets for anthracyclines such as DNA, cell membranes, or enzymes like topoisomerases could be involved, mechanisms by which these compounds exert their cytotoxic and differentiating effects remain unclear. Studies of correlation between the biological effects of anthracyclines and drug uptake have given conflicting conclusions. For example, a decrease in drug cytotoxicity for different incubation temperatures has been observed in spite of the same intracellular anthracycline amount, suggesting that temperature-dependent cytotoxic effects may be mediated by drug interaction with the cell membrane. What we propose in this review are results of our laboratory which are in agreement with an action mechanism targeted to the nucleus. In fact, we have shown by using microspectrofluorometry, that identical nuclear anthracycline concentration induces the same degree of cytotoxicity, independent of cellular MDR phenotype and the anthracycline structure. Thus, we could acquire information on the mechanisms of drug resistance related to drug transport. We could also give evidence that this accumulation is increased when MDR modulators, such as verapamil and S9788 and cyclosporin A or anthracyclines are used. For clinical applications, our studies have already dealt with nuclear concentration measurements of doxorubicin in leukocytes of treated patients, and in vitro measurements of drug efflux from nuclei of acute leukemic cells and its correlation with P-glycoprotein expression. However, in these studies, there was no correlation between anthracycline nuclear accumulation in vitro and P-glycoprotein expression. In addition, from preliminary results, we have shown that some modulators such as quinine do not significantly increase nuclear accumulation of anthracyclines in MDR cells but are able to restore anthracycline sensitivity. Other authors have recently shown that quinine has a relatively weak effect on cellular doxorubicin accumulation in MDR cells but is able to completely restore doxorubicin sensitivity. They concluded that quinine has essentially intracellular targets involved in drug distribution (cytoplasm --> nucleus) from sequestration compartments. Our data contradict this and we believe that such modulator modifies the molecular environment of anthracyclines and/or their binding to a possible cytoplasmic target leading to different cell death. Thus, we conclude that mechanisms by which anthracyclines induce cell death, and ways by which chemotherapy fails in resistant cells remain complex and are related to more than one target.

Antibiotics, Antineoplastic↗
PubMed1997

Characterization of acidic vesicles in multidrug-resistant and sensitive cancer cells by acridine orange staining and confocal microspectrofluorometry.

To study the pH gradient status through membranes of acidic vesicles, either in sensitive or in multidrug-resistant living cancer cells, we monitored the fluorescence-emission spectra of acridine orange. Successive stainings with a pH-sensitive dye and AO showed that low-pH organelles were stained red by AO. In these compartments, high AO concentrations are driven by the pH gradient through membrane vesicles. The resulting rise in the dye's oligomeric/monomeric ratio induced an increase in the red/green (655-nm/530-nm) emission intensity ratio. Therefore, the accumulation of AO in acidic organelles was appraised by determination of the contribution of the red emission intensity (R%) in each emission spectrum, using laser scanning confocal microspectrofluorometry. In vesicles of multidrug-resistant K562-R cells, R% is significantly higher (72 +/- 10%) than the value (48 +/- 8%) from K562-sensitive cells (p < 0.001). This result is interpreted as a more important accumulation of AO in acidic cytoplasmic structures of resistant cells, which induces a shift from AO monomers (green emission) to self-associated structures (red emission). Equilibration of the pH gradient through acidic organelles was performed by addition of weak bases and carboxylic ionophores. Ammonium chloride (0.1 mM), methylamine (0.1 mM), monensine (10 microM), or nigericine (0.3 microM) all suppressed the initial difference of local AO accumulation between both cell lines. These agents decreased the red emission intensity for the resistant cell line but not for the sensitive one. The same effects were induced by 50 microM verapamil, a pleiotropic drug-resistance modulator. Our data allow the hypothesis of a higher pH gradient through membranes of acidic organelles, which would be a potential mechanism of multidrug resistance via the sequestration of weak bases inside these organelles.

Acridine Orange↗
PubMed1997

[Effect of quinine on the multiple drug resistance and intracellular distribution of pirarubicin in LR73 tumor cells: a comparative study with verapamil and S9788 by confocal laser microspectrofluorometry].

Effectiveness of chemotherapeutic treatment is limited by multidrug resistance (MDR) phenomenon mediated by the overexpression of P-glycoprotein 170 termed Pgp which serves as an efflux pump removing several types of cytostatic drugs from the MDR cells. Several small molecules, frequently lipophilic cations and weak bases, are able to reverse in vitro this resistance. Several studies have shown that MDR modulators interact with Pgp. However, some molecules do not interact with Pgp but are able to completely restore drug sensitivity (e.g., quinine). Bennis et al. (1995) have shown recently that in contrast to verapamil and S9788, quinine increases nuclear doxorubicin accumulation without modifying its intracellular concentration. From this work, the authors concluded that quinine has essentially intracellular targets involved in drug distribution (cytoplasm to nucleus) from sequestration compartments. Their results have been obtained using spectrofluorometry on cell populations and fluorescence microscopy. By using confocal laser microspectrofluorometry, we investigated restoration of nuclear THP-DOX accumulation and sensitivity by verapamil, S9788 and quinine in 2 variants of the Chinese hamster ovary cells LR73, selected for resistance to doxorubicin (LR73D) and transfected with the mdr1 gene (LR73R), as well as in the sensitive ones (LR73S). Results show that verapamil and S9788 were able to restore THP-DOX sensitivity in resistant cells by increasing nuclear THP-DOX accumulation. This restoration is the consequence of Pgp inhibition and redistribution of the anticancer drug from the cytoplasm to nucleus. Quinine, in contrast, restores the sensitivity of MDR cells to THP-DOX and decreased their resistance index, but has no effect on THP-DOX nuclear accumulation. This suggests that quinine modifies the molecular environment of anthracyclines and/or their binding to cytoplasmic targets involved in another mechanism of anthracycline action.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Intracellular molecular interactions of antitumor drug amsacrine (m-AMSA) as revealed by surface-enhanced Raman spectroscopy.

Cytotoxicity of several classes of antitumor DNA intercalators is thought to result from disturbance of DNA metabolism following trapping of the nuclear enzyme DNA topoisomerase II as a covalent complex on DNA. Here, molecular interactions of the potent antitumor drug amsacrine (m-AMSA), an inhibitor of topoisomerase II, within living K562 cancer cells have been studied using surface-enhanced Raman (SER) spectroscopy. The work is based on data of the previously performed model SER experiments dealing with amsacrine/DNA, drug/topoisomerase II and drug/DNA/topoisomerase II complexes in aqueous buffer solutions. The SER data indicated two kinds of amsacrine interactions in the model complexes with topoisomerase II alone or within ternary complex: non-specific (via the acridine moiety) and specific to the enzyme conformation (via the side chain of the drug). These two types of interactions have been both revealed by the micro-SER spectra of amsacrine within living K562 cancer cells. Our data suppose the specific interactions of amsacrine with topoisomerase II via the side chain of the drug (particular feature of the drug/topoisomerase II and ternary complexes) to be crucial for its inhibitory activity.

Amsacrine↗
PubMed1996

DNA topoisomerase I changes the mode of interaction between camptothecin drugs and DNA as probed by UV-resonance Raman spectroscopy.

Pronounced differences of interactions of camptothecin (CPT) and its derivative 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT11), inhibitors of DNA topoisomerase I, with oligonucleotides were found using UV resonance Raman spectroscopy. 30-mer oligonucleotides were derived from the sequences of the topoisomerase I-induced and CPT-enhanced cleavage sites in SV40 DNA. CPT induces well-defined alterations of the oligo structure, whereas CPT11 interacts with oligonucleotides more weakly and in another manner than CPT. Formation of cleavable ternary complexes between CPT11, topoisomerase I and oligonucleotides causes CPT11 to interact with oligonucleotides in the same fashion as was found for its parent compound CPT, and enhances this interaction as compared to CPT-oligonucleotide complexes. The data present evidence of molecular interactions of CPT11 with both other partners (topoisomerase I and oligonucleotide) of the ternary cleavable complex at the oligonucleotide-enzyme interface.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Spatial and temporal Mg2+ signaling in single human tracheal gland cells.

The combined use of Mag-indo-1 probe and laser confocal UV-microspectrofluorometry allowed us to investigate the spatial and temporal dynamic changes of the Mg2+ variations in human tracheal gland (HTG) cells at the single cell level. Stimulation of HTG cells with either bradykinin, ouabain or extracellular high Mg2+ concentrations (up to 10 mM) induced increases in intracellular Mg2+ concentration [Mg2+]i. From a cytosolic basal concentration of 0.8 +/- 0.3 mM in a medium free of Mg2+, an increase in extracellular Mg2+ concentration from 1 to 10 mM, increased cytosolic [Mg2+]i from 1.4 +/- 0.6 to 1.8 +/- 0.8 mM after 10 min (p < 0.05). We also demonstrated using line-scanned spectral images within single cells, that the [Mg2+]i is distributed uniformally in the nucleoplasm, but in contrast, showed marked local differences among different cytoplasmic regions, thus suggesting a functional heterogeneity in the intracellular Mg2+ stores involved. The influx pathway for Mg2+ in HTG cells was not inhibited by verapamil and appeared to be independent of [Ca2+]i.

Bombesin↗
PubMed1996

Intracellular free Ca2+ dynamic changes to histamine are reduced in cystic fibrosis human tracheal gland cells.

This study documents a difference between cystic fibrosis human (CF-HTG) and normal human (HTG) tracheal gland cells: the ability of histamine to induce an increase of intracellular free calcium concentration [Ca2+]i was abnormally reduced in CF-HTG cells. The magnitude of the [Ca2+]i peak rise in response to histamine is smaller in CF-HTG cells than in HTG cells, and the percentage of CF-HTG cells that increase [Ca2+]i is decreased compared with HTG cells. In contrast to histamine, the human neutrophil elastase (HNE) stimulation of both CF-HTG and HTG cells generated [Ca2+]i asynchronous oscillations and the magnitude of the peak [Ca2+]i response as well as the percentage of responding cells were similar for both groups. By videomicroscopy observations, the secretory response (exocytosis of secretion granules) of CF-HTG cells occurred with HNE, but not with histamine, thus suggesting that [Ca2+]i asynchronous oscillations may be linked to the exocytosis process in human tracheal gland cells.

Calcimycin↗