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S Jiang

Publications and source records attributed to S Jiang.

At least 37 records · Page 2Linked to original sources
PubMed2003

Estrogen receptor corepressors -- a role in human breast cancer?

Estrogen receptor alpha (ERalpha) has an established role in promoting breast cancer. Transcriptional activation by ERalpha is a complex and multistep process, and it is influenced by coactivator and corepressor proteins that can either positively or negatively modulate ERalpha-mediated transcriptional activity. Corepressors are proposed to provide a counterbalance to the estrogen-induced transactivation, and represent a potential mechanism employed by the cell to regulate hormonal responses. In this review, we present evidence from tissue culture, animal and clinical studies, supporting the hypothesis that corepressors are crucial regulators of ERalpha-mediated action, and that their loss could promote breast cancer development and resistance to endocrine therapy. We propose that ERalpha corepressors play an important biological role by controlling the magnitude of the estrogen response, mediating antiestrogen inhibition of ERalpha, repressing DNA-bound ERalpha in the absence of the ligand, and conferring active repression of ERalpha-downregulated genes. Different ERalpha corepressors regulate steroid receptor activity through a variety of mechanisms, including formation of multiprotein complexes that are able to affect chromatin remodeling, histone deacetylation, or basal transcription. Other mechanisms include competition with coactivators, interference with DNA binding and ERalpha homodimerization, alteration of ERalpha stability, sequestration of ERalpha in the cytoplasm, and effects on RNA processing. Most ERalpha corepressors can control the receptor's activity through more than one mechanism, and it is possible that the synergy between different pathways cooperates to fully inhibit ERalpha transcriptional activity, and create an integrated response to a variety of different cellular signaling pathways. We will discuss the role of corepressors in tumor suppression and the link they might present between ERalpha regulation and DNA repair. Finally, we will discuss major challenges in the field and speculate on the exciting findings that await us in the next few years.

Breast Neoplasms↗
PubMed2002

A quantitative immuno-electron microscopic study of dopamine terminals in forebrain regions of the domestic chick involved in filial imprinting.

The mediorostral neostriatum/hyperstriatum ventrale and neostriatum dorsocaudale of the domestic chick are crucially involved in filial imprinting and are major targets of mesotelencephalic dopaminergic projections. To better understand the functional role of dopamine in these forebrain regions, the ultrastructure of dopamine terminals was studied by serial section electron microscopy using immunohistochemical labeling with antibodies to tyrosine hydroxylase and dopamine. At light as well as electron microscopic level, dopamine and tyrosine hydroxylase-immunoreactive fibers were present at moderate densities in the mediorostral neostriatum/hyperstriatum ventrale and high densities in the neostriatum dorsocaudale. The frequency of tyrosine hydroxylase-immunoreactive profiles per unit area was significantly higher in the neostriatum dorsocaudale than in the mediorostral neostriatum/hyperstriatum ventrale. In both regions, tyrosine hydroxylase-immunoreactive terminals were relatively small, with mean areas of 0.55 microm(2) in the mediorostral neostriatum/hyperstriatum ventrale and 0.48 microm(2) in the neostriatum dorsocaudale. The majority of tyrosine hydroxylase-immunoreactive synapses were symmetrical (83% in the mediorostral neostriatum/hyperstriatum ventrale, 75% in the neostriatum dorsocaudale) as opposed to asymmetrical (17 and 25%, respectively), but there were also tyrosine hydroxylase-immunoreactive terminals which lacked clear synaptic specializations. The preferred targets of the synaptic tyrosine hydroxylase-immunoreactive terminals were dendritic shafts (64% in the mediorostral neostriatum/hyperstriatum ventrale, 63% in the neostriatum dorsocaudale) and less frequently dendritic spines (17 and 23%, respectively) or perikarya (19 and 14%, respectively). In both forebrain regions, immunoreactive terminals were often found in close apposition to unstained terminals making asymmetrical synapses. In conclusion, these results indicate that the ultrastructural features of dopamine terminals in the avian telencephalon are very similar to those described in mammals and that dopamine may exert its effects primarily by modulating excitatory inputs.

Animals↗
PubMed2002

Postnatal pre- and postexposure passive immunization strategies: protection of neonatal macaques against oral simian-human immunodeficiency virus challenge.

Simian-human immunodeficiency viruses (SHIV) allow the evaluation of antiviral strategies that target the envelope glycoproteins of the human immunodeficiency virus 1 (HIV-1) in macaques. We previously protected neonates from oral challenge with cell-free SHIV-vpu+ by passive immunization with synergistic human neutralizing monoclonal antibodies (mAbs) (Baba et al., Nat Med 6:200-206, 2000). mAbs were administered prenatally to pregnant dams and postnatally to the neonates. Here, we used solely postnatal or postexposure mAb treatment, thus significantly reducing the amount of mAbs necessary. All neonatal monkeys were also protected with these abbreviated mAb regimens. Our results are directly relevant for humans because we used mAbs that target HIV-1 envelope glycoproteins. Thus, the large-scale use of passive immunization with neutralizing mAbs may be feasible in human neonates. The mAbs, being natural human proteins, can be expected to have low toxicity. Passive immunization has promise to prevent intrapartum as well as milk-borne virus transmission from HIV-1-infected women to their infants.

Administration, Oral↗
PubMed2001

Linkage studies between attention-deficit hyperactivity disorder and the monoamine oxidase genes.

Attention-deficit hyperactivity disorder (ADHD) is a prevalent behavioral disorder in children and the etiology of this disorder is not clear. Molecular genetic and pharmacological studies suggest the involvement of dopaminergic and noradrenergic neurotransmitter systems in ADHD, e.g., several reports have found association between ADHD and the dopamine receptor gene DRD-4, the dopamine transporter gene DAT1, and the catecholamine clearance enzyme catechol-O-methyltransferase. Monoamine oxidase (MAO) A and B genes encode enzymes that participate in the metabolism of neurotransmitters of the dopaminergic and noradrenergic systems. MAO inhibitors have been shown to be effective in the treatment of ADHD. Our previous studies showed an association between ADHD and the DXS7 locus, which is located in close vicinity to the MAO genes on chromosome X. These findings suggest that there might be linkage between ADHD and MAO genes. To test this hypothesis, we used the transmission/disequilibrium test (TDT) to test for linkage between a VNTR polymorphism at the MAOA(CA)(n) or MAOB(GT)(n) locus and DSM-III-R-diagnosed ADHD in 82 nuclear families of the Chinese population. The TDT analysis revealed linkage between ADHD and the MAOA(CA)(n) locus (chi-square = 15.25, df = 7, P < 0.05), but not the MAOB(GT)(n) locus (chi-square = 11.18, df = 7, P > 0.05). The data showed that ADHD was in linkage with the MAOA gene and suggested that MAOA might be a susceptibility factor for ADHD.

Alleles↗
PubMed2001

[Five de novo forms of polymorphisms first found in Chinese mitochondrial genome].

OBJECTIVE: To know more polymorphic changes in mitochondrial genome in Chinese. METHOD: PCR and sequencing of the 16,569 bp long mtDNA of the white blood cell DNA were conducted on 4 Chinese children, 3 with Rett syndrome and one normal. PCR and Restriction endonuclease digest, including artificial created restriction site (ACRS), were done on 100 normal controls in the light of the 7 newly discovered single base substitution sites. RESULT: Five point mutations, C298T, C638G, C3206T, A6323G and C6326T, neither appearing in MITOMAP database nor reported in literature before, were identified in Chinese people with the frequencies of 17.65%, 32.04%, 62.77%, 33.33% and 32.26%. Other two point mutations, C737T and C9860T, were found only in patients with Rett syndrome. CONCLUSION: The five sequence changes newly found in mitochondrial genome of Chinese are de novo kinds of polymorphism.

Child↗
PubMed2001

[Experimental observation of antagonism of polyaspartic acid against gentamicin-induced phospholipidosis in cochlea of guinea pig].

OBJECTIVE: To observe the effect of polyaspartic acid (PAA) on gentamicin-induced disturbance of phospholipid metabolism in cochlea of Guinea pig. METHODS: Ninety-four Guinea pigs were divided into 4 groups administered with PAA, PAA + GM, GM, or normal saline respectively. Auditory brain-stem response (ABR) was recorded before and one, five and ten days after the experiment. High performance liquid chromatography (HPLC) was used to determinate the amount of phospholipid in cochlear tissue, and ultrastructural change of lysosomes in the cochlear hair cells was observed by transmission electron microscopy one, five, and ten days after the experiment. RESULTS: No difference in any indicator was found one day after the beginning of experiment in all groups. The amounts of phosphatidylinositol (PI) and phosphatidylinositol-phosphate (PIP) increased significantly five days after administration of GM (19.7 micrograms +/- 6.6 micrograms and 121 micrograms +/- 21 micrograms respectively). The amount of PIP increased significantly 10 days after administration of GM (126 micrograms +/- 8 micrograms). Transmission electron microscopy showed an increase of number and volume of lysosome in cochlear outer hair cells and appearance of Hensen's body five days after administration of GM. Such changes became more significant and some lysosomes broke in the 10th day. The ABR threshold began to increase 5 days after the administration of GM, and continued to increase with time. CONCLUSION: PAA has inhibitory effect on gentamicin-induced lysosomal phospholipidosis in cochlea of Guinea pig, thus inhibiting gentamicin-induce hearing loss.

Animals↗
PubMed2001

Lack of association between the tryptophan hydroxylase gene A218C polymorphism and attention-deficit hyperactivity disorder in Chinese Han population.

Previous studies have suggested that the serotonergic (5-HT) system might be involved in the development of Attention-deficit hyperactivity disorder (ADHD). ADHD is frequently characterized by aggressive and impulsive behavior, a major symptom associated with reduction in serotonergic function. The tryptophan hydroxylase (TPH) gene is a reasonable candidate for ADHD because it encodes the rate-limiting enzyme in the process of 5-HT biosynthesis. In this study, we examined the relationship between the A218C polymorphism in TPH gene and ADHD. Sixty-nine ADHD patients and their biological parents were investigated. The A218C polymorphism in intron 7 of TPH gene was detected by PCR-RFLP method. No allele or genotype concerned with this A218C polymorphism was found to be associated with ADHD when analyzed with the haplotype relative risk method. Therefore, our data indicate that the TPH gene A218C polymorphism may not be a susceptibility factor of ADHD in the Chinese Han population.

Alleles↗
PubMed2001

Functional analysis of Csk and CHK kinases in breast cancer cells.

In this report, we analyzed the expression and kinase activities of Csk and CHK kinases in normal breast tissues and breast tumors and their involvement in HRG-mediated signaling in breast cancer cells. Csk expression and kinase activity were abundant in normal human breast tissues, breast carcinomas, and breast cancer cell lines, whereas CHK expression was negative in normal breast tissues and low in some breast tumors and in the MCF-7 breast cancer cell line. CHK kinase activity was not detected in human breast carcinoma tissues (12 of 12) or in the MCF-7 breast cancer cell line (due to the low level of CHK protein expression), but was significantly induced upon heregulin (HRG) stimulation. We have previously shown that CHK associates with the ErbB-2/neu receptor upon HRG stimulation via its SH2 domain and that it down-regulates the ErbB-2/neu-activated Src kinases. Our new findings demonstrate that Csk has no effect on ErbB-2/neu-activated Src kinases upon HRG treatment and that its kinase activity is not modulated by HRG. CHK significantly inhibited in vitro cell growth, transformation, and invasion induced upon HRG stimulation. In addition, tumor growth of wt CHK-transfected MCF-7 cells was significantly inhibited in nude mice. Furthermore, CHK down-regulated c-Src and Lyn protein expression and kinase activity, and the entry into mitosis was delayed in the wt CHK-transfected MCF-7 cells upon HRG treatment. These results indicate that CHK, but not Csk, is involved in HRG-mediated signaling pathways, down-regulates ErbB-2/neu-activated Src kinases, and inhibits invasion and transformation of breast cancer cells upon HRG stimulation. These findings strongly suggest that CHK is a novel negative growth regulator of HRG-mediated ErbB-2/neu and Src family kinase signaling pathways in breast cancer cells.

Animals↗
PubMed2001

Autocrine cell suicide in a Burkitt lymphoma cell line (Daudi) induced by interferon alpha: involvement of tumor necrosis factor as ligand for the CD95 receptor.

The CD95 receptor, a member of the tumor necrosis factor (TNF) receptor superfamily, mediates signals for cell death on specific ligand or antibody engagement. It was hypothesized that interferon alpha (IFN-alpha) induces apoptosis through activation of the CD95-mediated pathway and that CD95 and ligands of the death domain may belong to the group of IFN-stimulated genes. Therefore, the effect of IFN-alpha on CD95-CD95L expression, on the release of TNF-alpha, and on TNF receptor 1 expression in an IFN-sensitive human Burkitt lymphoma cell line (Daudi) was investigated. After 5 days' incubation, apoptosis in 81% of IFN-alpha-treated Daudi cells was preceded by a release of TNF-alpha and an induction of CD95 receptor expression. Although supernatants of IFN-treated Daudi cells induced apoptosis of CD95-sensitive Jurkat cells, CD95L was undetectable on protein or on messenger RNA levels, and the weak initial expression of TNF receptor 1 increased only slightly during IFN treatment. Surprisingly, binding of TNF-alpha to CD95 was observed and confirmed by 3 different techniques-enzyme-linked immunosorbent assay using immobilized CD95:Fc-immunoglobulin G, immunoprecipitation assay using CD95 receptor precipitates of Daudi cells, and binding of sodium iodide 125-TNF-alpha to Daudi cells, which was strongly stimulated by IFN-alpha and inhibited by CD95L, CD95:Fc, unlabeled TNF-alpha, and anti-TNF-alpha antibody. Preincubation of Daudi cells with antagonists of the CD95-mediated pathway resulted in an inhibition of IFN-alpha-mediated cell death. The present investigation shows that IFN-alpha induces autocrine cell suicide of Daudi cells by a cross-talk between the CD95 receptor and TNF-alpha. The CD95 receptor can be considered a third TNF receptor, in addition to p55 and p75.

Antineoplastic Agents↗
PubMed2001

A bioactive somatostatin analog without a type II' beta-turn: synthesis and conformational analysis in solution.

A cyclic somatostatin analog [structure: see text] (1) has been synthesized. Biological assays show that this compound has strong binding affinities to somatostatin hsst2 and hsst5 receptor subtypes (5.2 and 1.2 nM, respectively, and modest affinity to hsst4 (41.1 nM)). Our conformational analysis carried out in DMSO-d6 indicates that this compound exists as two structures arising from the trans and cis configurations of the peptide bond between Phe7 and N-alkylated Gly8. However, neither conformer exhibits a type II' beta-turn. This is the first report of a potent bioactive somatostatin analog that does not exhibit a type II' beta-turn in solution. Molecular dynamics simulations (500 ps) carried out at 300 K indicate that the backbone of compound 1 is more flexible than other cyclic somatostatin analogs formed by disulfide bonds.

Amino Acid Sequence↗
PubMed2001

Iodide uptake in human anaplastic thyroid carcinoma cells after transfer of the human thyroid peroxidase gene.

Human thyroperoxidase (hTPO) is critical for the accumulation of iodide in thyroid tissues. Poorly differentiated and anaplastic thyroid tumours which lack thyroid-specific gene expression fail to accumulate iodide and, therefore, do not respond to iodine-131 therapy. We consequently investigated whether transfer of the hTPO gene is sufficient to restore the iodide-trapping capacity in undifferentiated thyroid and non-thyroid tumour cells. The human anaplastic thyroid carcinoma cell lines C643 and SW1736, the rat Morris hepatoma cell line MH3924A and the rat papillary thyroid carcinoma cell line L2 were used as in vitro model systems. Employing a bicistronic retroviral vector based on the myeloproliferative sarcoma virus for the transfer of the hTPO and the neomycin resistance gene, the C643 cells and SW1736 cells were transfected while the L2 cells and MH3924A cells were infected with retroviral particles. Seven recombinant C643 and seven SW1736 cell lines as well as four recombinant L2 and four MH3924A cell lines were established by neomycin selection. They were studied for hTPO expression using an antibody-based luminescence kit, followed by determination of the enzyme activity in the guaiacol assay and of the iodide uptake capacity in the presence of Na125I. Genetically modified cell lines expressed up to 1,800 times more hTPO as compared to wild type tumour cells. The level of hTPO expression varied significantly between individual neomycin-resistant cell lines, suggesting that the recombinant retroviral DNA was integrated at different sites of the cellular genome. The accumulation of iodide, however, was not significantly enhanced in individual recombinant cell lines, irrespective of low or high hTPO expression. Moreover, there was no correlation between hTPO expression and enzyme activity in individual cell lines. The transduction of the hTPO gene per se is not sufficient to restore iodide trapping in non-iodide-concentrating tumour cells. Future studies will have to concentrate on the possible expression of enzymatically active proteins or the transfer of multiple genes involved in iodide trapping.

Animals↗
PubMed2001

Glucose transport and apoptosis after gene therapy with HSV thymidine kinase.

The relation between tumour metabolism and induction of apoptosis by gene therapy was investigated in a rat Morris hepatoma (MH3924A) model expressing the HSV thymidine kinase (HSVtk) gene. In vivo the amount of glucose transporter (GLUT1 and GLUT3 isoforms) expressing cells was determined in tumours of untreated and treated animals using immunohistochemistry. In vitro uptake studies with 2-fluoro-2-deoxy-D-glucose (FDG), 3-O-methylglucose and thymidine (TdR) and a TUNEL (TdT-mediated dUTP nick end labelling) assay for the assessment of apoptosis were done immediately and 24 h after treatment of the recombinant cells with different doses of ganciclovir (GCV). Immunohistochemistry revealed a significant increase in GLUT1 in treated tumours which showed enhanced transport activity for FDG. In vitro the FDG and 3-O-methylglucose uptake increased to 186% when compared with that of the non-treated cells immediately after incubation with GCV. However, 24 h later the FDG uptake had declined to its normal level, whereas the accumulation of 3-O-methylglucose remained elevated. The uptake of TdR, which was determined simultaneously, decreased in the acid-insoluble fraction of the cells to 27% and 11%, respectively, immediately and 24 h after therapy, while in the acid-soluble fraction it increased to 229% and to 167%, respectively. Employing the TUNEL technique, 25% of cells were found to be apoptotic 24 h after the termination of GCV treatment. Inhibition of glucose transport by cytochalasin B or competition with deoxyglucose resulted in a 78% (cytochalasin B) and 88% (deoxyglucose) decrease in FDG uptake in the recombinant hepatoma cells and in an increase in the apoptotic cell fraction. It is concluded that inhibition of enhanced glucose transport in GCV-treated cells increased apoptosis. Therefore, enhanced glucose transport seems to represent a stress reaction of tumour cells dedicated for the prevention of cell death.

3-O-Methylglucose↗
PubMed2001

Indocyanine green effect on cultured human retinal pigment epithelial cells: implication for macular hole surgery.

PURPOSE: To evaluate potential toxic effects of indocyanine green dye on cultured human retinal pigment epithelial cells. METHODS: Controlled laboratory experiment. Cultured human retinal pigment epithelial cells were exposed to balanced saline solution, balanced saline solution with endoillumination, indocyanine green or indocyanine green with endoillumination. Cells were evaluated by light microscopy, electron microscopy, and a mitochondrial dehydrogenase assay. RESULTS: Retinal pigment epithelial cells exposed to indocyanine green showed no histologic or ultrastructural changes. Those exposed to indocyanine green alone or indocyanine green plus light demonstrated a significant decrease in mitochondrial enzyme activity (P = 0.0002 and 0.005, respectively). CONCLUSION: Brief exposure of cultured human retinal pigment epithelial cells to indocyanine green results in decreased mitochondrial enzyme activity but does not appear to influence cellular morphology or ultrastructure.

Cells, Cultured↗
PubMed2001

Potentiation of cytotoxicity of adriamycin on human ovarian carcinoma cell line 3AO by low-level ultrasound.

The aim of this study was to determine whether the ultrasound, with a dosage that did not lead to acute and delayed inhibition, could potentiate the cytotoxicity of adriamycin to human ovarian carcinoma cell line 3AO in vitro. Drug sensitivity was analyzed by clonogenic assay, cells were treated by adriamycin singly in group ADM (control), adriamycin prior to ultrasound exposure in group ADM + US, and ultrasound irradiation prior to adriamycin administration in group US + ADM. The intracellular drug accumulation in each group was determined by fluorometry. The results were: (1) the values of IC50 were 0.0083, <0.001 and 0.0065 microg/ml in group ADM, ADM + US and US + ADM respectively; the clone surviving rate in group ADM + US and in group US + ADM were decreased (P < 0.001, P < 0.01), compared with control; the surviving rate in group ADM + US was lower than that in group US + ADM (P < 0.01). (2) The intracellular drug accumulations in group ADM + US were promoted (P < 0.01) and not increased significantly in group US + ADM (P > 0.05). These suggested that the low-level ultrasound could enhance the cytotoxicity of adriamycin to human ovarian carcinoma cells and promoted intracellular drug contents played the leading role.

Antineoplastic Agents↗
PubMed2001

Amplification and cloning of the full-length genome of Japanese encephalitis virus by a novel long RT-PCR protocol in a cosmid vector.

A novel and rapid full-length long RT-PCR technique was established to produce genome-length cDNA from Japanese encephalitis virus. In vitro positive strand RNA transcripts from the full-length RT-PCR amplicon including T7 promoter sequences at the 5' end were proved to be infectious upon transfection. The full-length amplicon without the T7 promoter was cloned into a cosmid vector under the SP6 promoter. This stable clone, designated as pJEV-1, was characterised further and used as a genetic resource for generation of infectious RNA transcripts, gene manipulation and expression. The 'run-off' transcript from pJEV-1 with vector sequences at the either end of the insert was not infectious, but transcripts of the full-length PCR amplicon from pJEV-1 produced infectious virus upon transfection. A transcript with an engineered Xho I site from two ligated PCR fragments amplified from pJEV-1 was also infectious. Furthermore, the coding region for premembrane and envelope proteins (preM-E) from pJEV-1 was subcloned and expressed in the Drosophila Expression System. The expressed protein showed correct molecular size and was immunoreactive with a Japanese encephalitis virus E protein-specific antibody. The derivation of genome-size cDNA from Japanese encephalitis virus and the stable clone will facilitate investigation of this virus and elucidation of its pathogenesis at the molecular level.

Animals↗
PubMed2001

Circulating natural IgM antibodies and their corresponding human cord blood cell-derived Mabs specifically combat the Tat protein of HIV.

OBJECTIVE: IgM antibodies reactive with each of two specifically defined sequences of HIV Tat protein have been identified in sera from both HIV(+) and normal (HIV(-)) humans. This study was designed to confirm that those antibodies are innate immune factors capable of restriction of specific mechanisms of HIV pathogenicity attributed to the Tat protein. MATERIALS AND METHODS: Antibody-secreting hybridomas were generated from human cord blood cells and processed for monoclonality. Those Mabs reactive with each of the sequences of Tat with which the circulating antibodies are reactive were isolated and their heavy and light chains identified and DNA sequenced. Pools of IgM isolated from blood of normal humans, chimpanzees, rhesus macaques, and mice and the isolated Tat reactive Mabs were tested for capacity to inhibit Tat-induced human T-cell apoptosis. RESULTS: Human and chimpanzee IgM pools, as well as the human cord blood cell-derived Mabs, showed a definite capacity to inhibit the Tat-induced apoptosis, while the IgM pools of rhesus macaques or of mice did not. CONCLUSIONS: These studies establish that the circulating IgM of normal humans include innate antibodies capable of restriction of HIV Tat-induced pathogenesis. That capacity is shared by chimpanzee IgM but not by IgM of other primates or of mice. The identification of those human circulating antibodies as innate is confirmed by the display of similar epitopic identity and apoptosis inhibition capacity by Mabs from human cord blood cell hybridomas. Thus, the arsenal of human cord blood cell hybridomas provides a resource by which, specifically, the potential therapeutic role of the identified HIV Tat-reactive Mabs and, broadly, the fundamental role of innate antibodies in infection control may be explored.

Adult↗
PubMed2001

Glutamate induced modulation of free Ca(2+) in isolated inner hair cells of the guinea pig cochlea.

To explore the possible involvement of glutamate (Glu) in modulation of inner hair cell (IHC) functions, the glutamate (Glu) induced changes in intracellular free Ca(2+) ([Ca(2+)]i) concentration in isolated IHCs and outer hair cells (OHCs) of the guinea pig cochlea were investigated with fluo-3, a fluorescent probe for intracellular Ca(2+). Their unique flask shape identified the IHCs with a distinct neck and spherical base with a large spherical nucleus. Normal cell shapes could be maintained for about 2 h. Fluorescence of fluo-3 was distributed in the whole isolated IHC with brighter staining nuclei. Static [Ca(2+)]i remained constant within the observation period in the absence of Glu. In the presence of a low concentration of Glu (3.85 microM), there was an increase of [Ca(2+)]i in IHCs, whereas no obvious [Ca(2+)]i change was found in OHCs. The increase of the fluorescence in IHCs reached peak level at 180 s and then gradually reduced at 400 s after the administration of Glu. The increases of [Ca(2+)]i were observed in nine of 10 IHCs, but one IHC did not show any change. For 10 of the observed OHCs, seven showed no [Ca(2+)]i change, and three showed minor reduction of [Ca(2+)]i. The increase of the Glu concentration resulted in a corresponding change of [Ca(2+)]i in the IHCs after three times administration of Glu. These results suggest that Glu acts on the IHCs presynaptic autoreceptor in a positive feedback manner.

Animals↗