Biomedical subjects

E H Lee

Publications and source records attributed to E H Lee.

At least 19 recordsLinked to original sources

PubMed1999

Glibenclamide induces apoptosis through inhibition of cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels and intracellular Ca(2+) release in HepG2 human hepatoblastoma cells.

Glibenclamide, an inhibitor of cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels, induced apoptosis in a dose- and time-dependent manner in HepG2 human hepatoblastoma cells. Glibenclamide increased intracellular Ca(2+) concentration, which was significantly inhibited by Ca(2+) release blockers dantrolene and TMB-8. BAPTA/AM, an intracellular Ca(2+) chelator, and the Ca(2+) release blockers significantly inhibited glibenclamide-induced apoptosis. Glibanclamide also increased intracellular Cl(-) concentration, which was significantly blocked by CFTR Cl(-) channel activators levamisole and bromotetramisole. These activators also significantly inhibited both intracellular Ca(2+) release and apoptosis induced by glibenclamide. The expression of CFTR protein in the cells was confirmed by Western blot analysis. These results suggest that glibenclamide induced apoptosis through inhibition of CFTR Cl(-) channels and intracellular Ca(2+) release and that this protein may be a good target for treatment of human hepatomas.

Apoptosis↗

PubMed1999

Corticotropin-releasing factor enhances brain-derived neurotrophic factor gene expression to facilitate memory retention in rats.

In the present study, we investigated the effects of corticotropin-releasing factor (CRF) injected into the dentate gyrus (DG) of the hippocampus on brain-derived neurotrophic factor (BDNF) mRNA expression and studied whether N-methyl-D-aspartate (NMDA) receptor mediates the effects of CRF on BDNF mRNA expression in the DG. Since both CRF and BDNF gene expressions are involved in memory processing in rats, we further investigated whether CRF facilitates memory retention through enhanced BDNF mRNA expression in the hippocampus. Effect of direct BDNF injection to the DG on retention performance in rats was also assessed. Results indicated that intra-DG CRF injection produced a dose-dependent (0.1 microg, 1.0 microg and 10 microg) increase in BDNF mRNA level, while intra-DG MK801 injection produced a dose-dependent (0.08 microg, 0.2 microg and 2.0 microg) decrease in BDNF mRNA expression in the DG. MK801, at a dose having no significant effect alone (0.08 microg), significantly antagonized the effect of CRF on BDNF mRNA expression. On the other hand, CRF (1.0 microg) consistently and markedly improved retention performance in rats in an inhibitory avoidance learning task. BDNF antisense oligonucleotide treatment, at a concentration which did not affect retention performance alone (0.5 mM), blocked the memory-enhancing effect of CRF. However, direct and chronic BDNF injection to the DG did not improve memory performance in rats. These results together suggest that at least one of the mechanisms responsible for the memory-facilitating effect of CRF is mediated through enhanced BDNF mRNA expression in the hippocampus. The lack of an effect of intra-DG BDNF injection on memory retention is also discussed.

Animals↗

PubMed1999

The evaluation of the antianaphylactic effect of Oryza sativa L. subsp. hsien Ting in rats.

We studied the effect of the methanol extract of Oryza sativa L. subsp. hsien Ting (OSHT) on anaphylaxis. OSHT (0.001-1.0 mg g-1body weight (BW)) dose-dependently inhibited systemic anaphylaxis induced by compound 48/80 in rats. When OSHT was pretreated at concentrations ranging from 0.001 to 1.0 mg g-1BW, the serum histamine levels were reduced in a dose-dependent manner. OSHT (0. 001-1.0 mg g-1BW) also inhibited local anaphylaxis activated by anti-dinitrophenyl (DNP) IgE. Moreover, OSHT dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cAMP in RPMC, when OSHT was added, significantly increased approx. 20-fold compared with that of basal cells. These results indicate that OSHT possesses strong antianaphylactic activity by inhibition of histamine release from mast cells in vivo and in vitro.

Anaphylaxis↗

PubMed1999

Very long chain acyl coenzyme A dehydrogenase deficiency in a 5-month-old Korean boy: identification of a novel mutation.

A 5-month-old Korean boy who presented with lethargy and cardiomyopathy was diagnosed with very long chain acyl coenzyme A dehydrogenase (VLCAD) deficiency by organic acid, fatty acid, acylcarnitine, and molecular genetic analysis. The patient was a compound heterozygote for mutations in the VLCAD gene. One allele contains a 3-bp deletion in exon 6, deleting glutamic acid in codon 130 (E130del ); this allele is of paternal origin. The patient's maternally derived allele is a novel mutation, C1843T in exon 20, which creates a premature termination codon (R615stop ). Although molecular genetic characterization of VLCAD deficiency is limited to a few patients, heterogeneity of mutations is already apparent. However, the E130del is a relatively frequent mutant allele, which has been noted in 2 previously identified patients. The 2 mutant alleles in our patient appear to be responsible for his severe and fatal clinical manifestations.

Acyl-CoA Dehydrogenase, Long-Chain↗

PubMed1999

Neuroprotective mechanism of glial cell line-derived neurotrophic factor on dopamine neurons: role of antioxidation.

Recombinant human GDNF was infused into the rat striatum either acutely or subchronically. Its effects and its interactions with MPP+ on antioxidant enzyme activities were examined. Results indicated that acute GDNF infusion significantly increased glutathione peroxidase, superoxide dismutase and catalase activities. Subchronic GDNF treatment decreased the DA level and enhanced DA turnover. Pre-treatment with GDNF markedly protected DA neurons against MPP+-induced toxicity. These results suggest that GDNF protects DA neurons through its activation of the antioxidant enzyme systems.

1-Methyl-4-phenylpyridinium↗

PubMed1999

Salviae radix root extract inhibits immunoglobulin E-mediated allergic reaction.

We investigated the effects of the aqueous extract of Salviae radix root (SRRAE) on immediate allergic reactions. SRRAE inhibited by 72.7% passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) immunoglobulin E (IgE). SRRAE dose dependently inhibited histamine release and tumor necrosis factor-alpha production from the rat peritoneal mast cells (RPMCs) by anti-DNP IgE. However, SRRAE showed no significant inhibitory effect on compound 48/80-induced systemic allergic reaction and histamine release from RPMCs. The level of cAMP in RPMCs, when SRRAE was added, significantly increased compared with that of a normal control. These results indicate that SRRAE may contain compounds with actions that inhibit anti-DNP IgE-induced mast cell degranulation in rats.

Anaphylaxis↗

PubMed1999

Effect of Korean folk medicine 'Chung-Dae-San' on mast cell-dependent anaphylactic reaction.

We investigated the effect of the herbal formulation 'Chung-Dae-San' (CDS) on anaphylactic reactions. CDS inhibited compound 48/80-induced anaphylactic shock 100% with the dose of 10(0) g/kg body weight (BW). When CDS was given as pretreatment at concentrations ranging from 10(-4) to 10(0) g/kg BW, the serum histamine levels induced by compound 48/80 were reduced in a dose-dependent manner. We also investigated the effect of CDS on mast cell-dependent passive cutaneous anaphylaxis (PCA) activated by anti-dinitrophenyl (DNP) IgE antibody. CDS potently inhibited PCA when administered orally, topically, intraperitoneally or intradermally. However, it did not show inhibitory activity when administered intravenously. CDS dose-dependently inhibited the histamine release from the rat peritoneal mast cells (RPMC) by compound 48/80 and anti-DNP IgE. Moreover, the level of cAMP in RPMC, when CDS was added, significantly increased about 4-fold at 4 min compared with that of basal cells. These results indicate that CDS may possess strong antianaphylactic activity and also suggest the differential activity following administration routes may be caused by difference in bioavailability.

Anaphylaxis↗

PubMed1999

Degeneration and transdifferentiation of human lens epithelial cells in nuclear and anterior polar cataracts.

PURPOSE: To study the possible mechanisms of cataractogenesis by evaluating the characteristics of cataractous lens epithelial cells (LECs) in different types of human cataract. SETTING: Kangnam St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. METHODS: Lens epithelial cells attached to the anterior capsules in eyes with nuclear or anterior subcapsular were analyzed for morphological characteristics by electron microscopy and for cellular characteristics by immunohistochemistry. RESULTS: Human LECs beneath the anterior capsule were degenerated in nuclear cataracts and were transdifferentiated in anterior polar cataracts. In senile nuclear cataractous lenses, LECs beneath the anterior capsule showed degenerative changes in morphology. In nuclear cataracts, LECs were immunohistochemically positive for cytokeratin and vimentin, while those in anterior polar cataracts were positive for vimentin only. The LECs of anterior subcapsular cataracts were transdifferentiated into spindle-shaped fibroblast-like cells without cellular junctions and embedded within a fibrillar meshwork mass. The extracellular matrixes in the anterior capsule of anterior subcapsular cataracts were immunohistochemically positive for fibronectin, laminin, collagen type I, and collagen type IV. CONCLUSIONS: Lens epithelial cells in different types of cataracts have distinct cellular characteristics and may possess a bipotential nature with the ability to transdifferentiate into mesenchymal cells. This may be an underlying mechanism for the development of cataract and capsule opacification.

Adult↗

PubMed1999

The farAB-encoded efflux pump mediates resistance of gonococci to long-chained antibacterial fatty acids.

Gonococci often infect mucosal surfaces bathed in antibacterial fatty acids (FAs). Resistance of gonococci to FAs and other antibacterial hydrophobic agents has been attributed to the mtrCDE-encoded efflux pump system and a heretofore undefined mechanism. This alternative resistance mechanism has been suggested to mediate gonococcal resistance to long-chained FAs independently of the mtr efflux pump. We have now identified this alternative FA resistance system in gonococci and report that it bears significant similarity to the emrAB-encoded efflux pump possessed by Escherichia coli and the vceAB-encoded pump of Vibrio cholerae. We termed the gonococcal version of this efflux pump farAB (fatty acid resistance) to signify its involvement in FA resistance expressed by gonococci and to distinguish it from the emrAB- or vceAB-encoded pumps that modulate bacterial susceptibility to uncoupling agents and certain antibiotics. Although the farAB system in gonococci was found to provide resistance to FAs independently of the mtrCDE-encoded efflux pump, its function was dependent on the MtrE outer membrane protein. Moreover, expression of the tandemly linked farA and farB genes was positively associated with the presence of the MtrR transcriptional regulatory protein that normally downregulates the expression of mtrCDE. Thus, the data presented herein suggest that, while the mtrCDE- and farAB-encoded systems act independently to mediate resistance of gonococci to host-derived, hydrophobic antimicrobial agents, their capacity to export these agents is dependent on the same outer membrane protein (MtrE), and their expression may be differentially controlled by the same transcriptional regulatory protein (MtrR).

Amino Acid Transport Systems, Neutral↗

PubMed1999

Decreased azithromycin susceptibility of Neisseria gonorrhoeae due to mtrR mutations.

Single-dose azithromycin therapy has recently been used in Uruguay for the treatment of uncomplicated gonococcal infections. As part of an active surveillance study to monitor the emergence of antibiotic resistance in gonococcal isolates, we examined the levels of azithromycin susceptibility in 51 consecutive isolates obtained from males with uncomplicated gonococcal urethritis. Isolates with decreased susceptibility to azithromycin (MICs, 0.25 to 0.5 microg/ml) were common, and these isolates often displayed cross-resistance to hydrophobic antimicrobial agents (erythromycin and Triton X-100). Resistance to erythromycin and Triton X-100 is frequently due to overexpression of the mtrCDE-encoded efflux pump mediated by mutations in the mtrR gene, which encodes a transcriptional repressor that modulates expression of the mtrCDE operon. Accordingly, we questioned whether clinical isolates that express decreased azithromycin susceptibility harbor mtrR mutations. Promoter mutations that would decrease the level of expression of mtrR as well as a missense mutation at codon 45 in the mtrR-coding region that would result in a radical amino acid replacement within the DNA-binding motif of MtrR were found in these strains. When these mutations were transferred into azithromycin-susceptible strain FA19 by transformation, the susceptibility of gonococci to azithromycin was decreased by nearly 10-fold. The mtrCDE-encoded efflux pump system was responsible for this property since insertional inactivation of the mtrC gene resulted in enhanced susceptibility of gonococci to azithromycin. We conclude that the mtrCDE-encoded efflux pump can recognize azithromycin and that the emergence of gonococcal strains with decreased susceptibility to azithromycin can, in part, be explained by mtrR mutations.

Anti-Bacterial Agents↗

PubMed1999

Novel roles of specific isoforms of protein kinase C in activation of the c-fos serum response element.

Protein kinase C (PKC) is a multigene family of enzymes consisting of at least 11 isoforms. It has been implicated in the induction of c-fos and other immediate response genes by various mitogens. The serum response element (SRE) in the c-fos promoter is necessary and sufficient for induction of transcription of c-fos by serum, growth factors, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). It forms a complex with the ternary complex factor (TCF) and with a dimer of the serum response factor (SRF). TCF is the target of several signal transduction pathways and SRF is the target of the rhoA pathway. In this study we generated dominant-negative and constitutively active mutants of PKC-alpha, PKC-delta, PKC-epsilon, and PKC-zeta to determine the roles of individual isoforms of PKC in activation of the SRE. Transient-transfection assays with NIH 3T3 cells, using an SRE-driven luciferase reporter plasmid, indicated that PKC-alpha and PKC-epsilon, but not PKC-delta or PKC-zeta, mediate SRE activation. TPA-induced activation of the SRE was partially inhibited by dominant negative c-Raf, ERK1, or ERK2, and constitutively active mutants of PKC-alpha and PKC-epsilon activated the transactivation domain of Elk-1. TPA-induced activation of the SRE was also partially inhibited by a dominant-negative MEKK1. Furthermore, TPA treatment of serum-starved NIH 3T3 cells led to phosphorylation of SEK1, and constitutively active mutants of PKC-alpha and PKC-epsilon activated the transactivation domain of c-Jun, a major substrate of JNK. Constitutively active mutants of PKC-alpha and PKC-epsilon could also induce a mutant c-fos promoter which lacks the TCF binding site, and they also induce transactivation activity of the SRF. Furthermore, rhoA-mediated SRE activation was blocked by dominant negative mutants of PKC-alpha or PKC-epsilon. Taken together, these findings indicate that PKC-alpha and PKC-epsilon can enhance the activities of at least three signaling pathways that converge on the SRE: c-Raf-MEK1-ERK-TCF, MEKK1-SEK1-JNK-TCF, and rhoA-SRF. Thus, specific isoforms of PKC may play a role in integrating networks of signal transduction pathways that control gene expression.

3T3 Cells↗

PubMed1999

The nitric oxide-producing properties of Ulmi radicis cortex extract.

We investigated the effect of Ulmi radicis cortex extract (UrCE) on the production of nitric oxide (NO). Stimulation of mouse peritoneal macrophages with UrCE after the treatment of recombinant interferon-gamma (rIFN-gamma) resulted in the increased NO synthesis. UrCE had no effect on NO synthesis by itself. When UrCE was used in combination with rIFN-gamma, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. The optimal effect of UrCE on NO synthesis was shown 6 h after treatment with rIFN-gamma. NO production was inhibited by NG-monomethyl-L-arginine. The increased production of NO from rIFN-gamma plus UrCE-stimulated cells was decreased by the treatment of protein kinase C inhibitor such as staurosporin. In addition, synergy between rIFN-gamma and UrCE was mainly dependent on UrCE-induced tumor necrosis factor-alpha (TNF-alpha) secretion. All the preparations of UrCE were endotoxin free. These results suggest that the capacity or UrCE to increase NO production from rIFN-gamma-primed mouse peritoneal macrophages is the result of UrCE-induced TNF-alpha secretion.

Animals↗

PubMed1999

Noise level of drilling instruments during mastoidectomy.

Exposure to intense noise has been identified as a potential risk in the development of hearing impairment. Social concern about excessive noise is increasing and this also extends to the operating room. A noise level study was performed in the operating room during mastoidectomy with a sound level meter and it was analyzed by a sound-analyzing program. The drilling instruments used included the Stryker, Midas, M.P.S. and Med-Next. The operator was exposed to sound levels from 69 to 83 dBA. The loudest drilling instrument was the Midas and it produced an average sound level of 83 dBA to the operator. The mean exposure time was 41 minutes during mastoidectomy. This is below the occupational noise-level regulations in Korea. However, considering that individual susceptibility to noise varies and that the otologic surgeon is repeatedly exposed to prolonged drilling noise, ear protection is recommended for the operators of high-speed drilling instruments.

Chronic Disease↗

PubMed1999

Reactive oxygen species-induced apoptosis and necrosis in bovine corneal endothelial cells.

PURPOSE: The loss of corneal endothelial cells associated with aging and possibly other causes has been speculated to be related to exposure to reactive oxygen species (ROS). The current study was conducted to investigate, by use of photosensitizers, the underlying mechanisms involved in the death of bovine corneal endothelial cells (BCENs) caused by ROS. METHODS: BCEN cells in primary culture were treated with a photosensitizer (riboflavin or rose bengal) with light exposure. The patterns of cell damage and death were assessed using an acridine orange-ethidium bromide differential staining method, TdT-mediated dUTP nick-end labeling (TUNEL) assay, and transmission electron microscopy. The cytotoxicity was assayed by mitochondrial function using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) testing. Antioxidants, including catalase, L-histidine, salicylic acid, and superoxide dismutase, were used to determine the types of ROS involved. Activation of nuclear factor (NF)-kappaB was examined by fluorescent immunocytochemistry with anti-p65 antibody. RESULTS: Light-irradiated riboflavin or rose bengal resulted in a significant decrease in viability of BCEN cells. Chromosomal condensation and fragmentation were observed in apoptotic cells, and membrane lysis and damage of cell ultrastructures were observed in necrotic cells. Riboflavin induced apoptosis at 30 minutes and thereafter and induced necrosis after 2 hours. Rose bengal was shown to cause similar effects within half the time required for the effects of riboflavin. Catalase and salicylic acid were found to provide protection for BCENs from cytotoxic effects of riboflavin, and L-histidine was found to protect BCENs from cytotoxicity induced by rose bengal. Kinetic studies using immunocytochemistry showed that NF-kappaB was translocated into the nucleus within 15 minutes and 30 minutes after treatment with rose bengal and riboflavin, respectively. CONCLUSIONS: The cytotoxic effects of photo-irradiated riboflavin and rose bengal are shown to be mediated by two distinct but parallel pathways, one leading to apoptosis and the other to necrosis. Possible involvement of NF-kappaB in cell death is suggested. These findings provide potential leads for future investigation into the molecular mechanisms of loss of corneal endothelial cells related to aging, oxidative stress, and possibly other similar causes.

Acridine Orange↗

PubMed1999

Role of transforming growth factor-beta in transdifferentiation and fibrosis of lens epithelial cells.

PURPOSE: To determine the levels of mRNAs encoding markers of fibrosis in lens epithelial cells (LECs) from patients with anterior polar cataracts and to test whether transforming growth factor (TGF)-beta enhances the expression of mRNAs for mesenchymal markers in LECs. METHODS: LECs attached to the anterior capsules of patients with nuclear or anterior polar cataracts were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) for the expression of mRNAs encoding pathologic extracellular matrix proteins, a marker of myofibroblast transformation, growth factors, and growth factor receptors, and by western blot analysis for the proteins encoded by these mRNAs. Bovine lens epithelial explants and intact rabbit lenses cultured with or without TGF-beta1 were also subjected to RT-PCR and western blot analysis. RESULTS: The levels of fibronectin, type I collagen, and alpha-smooth muscle actin (SMA) mRNAs were higher in LECs from patients with anterior polar cataracts than in those from patients with nuclear cataracts. Expression of mRNAs for TGF-beta1, TGF-beta2, TGF-beta receptor type II, and connective tissue growth factor (CTGF) was significantly greater in anterior polar type than in nuclear type cataracts. In contrast, expression of mRNAs for epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), fibroblast growth factor (FGF)-2, and FGF receptor-1 was similar in LECs from the two types of cataracts. TGF-beta1 markedly increased the levels of fibronectin, type I collagen, and alpha-SMA mRNA in bovine lens epithelial explants and intact rabbit lenses. CONCLUSIONS: This is the first finding showing altered mRNA expression in LECs from anterior polar cataracts. Enhanced expression of TGF-beta and the TGF-beta receptor suggests that TGF-beta derived from LECs may function in an autocrine fashion as the prime mediator of transdifferentiation and pathogenesis in human LECs. Elevated levels of CTGF mRNA suggest that this growth factor may play a role in the increased deposition of extracellular matrix in metaplastic LECs.

Actins↗

PubMed1998

Enhanced glial cell line-derived neurotrophic factor mRNA expression upon (-)-deprenyl and melatonin treatments.

Glial cell line-derived neurotrophic factor (GDNF) has been shown to be a preferentially selective neurotrophic factor for dopamine (DA) neurons. In the present study, we have examined the distribution of GDNF mRNA expression in several major DA-containing cell body and terminal areas and the regulation of GDNF mRNA expression upon various pharmacological treatments. Results indicated that there is a relatively higher GDNF mRNA level in neurons of the nigrostriatal and mesolimbic dopaminergic pathways. Upon chronic 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) treatment (30 mg/ kg, i.p., for 7 days), DA level was decreased, whereas GDNF mRNA expression was increased in the striatum, suggesting that more GDNF is synthesized and expressed to cope with the neurotoxin insult. Furthermore, among several DA neuron protective and/or therapeutic agents examined, both intrastriatal injections of (-)-deprenyl (1.25 microg and 2.5 microg) and melatonin (30 microg, 60 microg, and 120 microg) significantly enhanced GDNF mRNA expression in the striatum, whereas the same concentrations of (-)-deprenyl did not affect monoamine oxidase B (MAOB) activity, although it increased glutathione peroxidase (GPx) and/or superoxide dismutase (SOD) activities. Similarly, the same concentrations of melatonin did not alter SOD or GPx activities, except that the highest dose of melatonin (120 microg) increased lipid peroxidation in the striatum. Conversely, GM1 ganglioside injection (45 microg) lacked of an effect on GDNF mRNA expression. Together, these results suggest that both (-)-deprenyl and melatonin up-regulate GDNF gene expression at threshold doses lower than that needed for altering MAOB activity and/or the antioxidant enzyme systems, respectively. These results provide new information on the neuroprotective and therapeutic mechanisms of (-)-deprenyl and melatonin on DA neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1998

Molecular cloning of a novel GTP-binding protein induced in fish cells by rhabdovirus infection.

We have cloned and sequenced a cDNA encoding GTP-binding protein from a fish cell, CHSE-214. The clone was 1493 bp long and contained an open reading frame encoding 364 amino acids. It has the five sequence motifs G1-G5 that are conserved in all GTP-binding proteins. Its amino acid sequences are strikingly different from those of the well-characterized G-proteins. However, sequences closely related to this protein are found in various kinds of species including human, Arabidopsis, Drosophila and archaebacteria, suggesting a novel subfamily within the superfamily of the GTP-binding proteins. Northern analysis indicates that this gene is constitutively expressed at a low level in normal cells but is induced by fish rhabdovirus infection at about 24 h post infection and disappears thereafter. Based on these observations, we propose that this protein represents an evolutionarily conserved novel subfamily of GTP-binding proteins which may play an important role in fish rhabdovirus infection.

Amino Acid Sequence↗

PubMed1998

Electrophysiological and behavioral effects of Tyr-D-Arg-Phe-Sar on locus coeruleus neurons of the rat.

The effect of Tyr-D-Arg-Phe-Sar (TAPS), a mu-selective tetrapeptide analog of dermorphin, was studied in the rat both in vitro, using slices of the locus coeruleus, and in vivo, after microinjection into the locus coeruleus. In electrophysiological studies, TAPS (1-100 nM) was able to inhibit spontaneous firing, cause hyperpolarization of the membrane potential and reduce the input resistance of neurons of the locus coeruleus, suggesting that there was an effect on the potassium channels. Based on the inhibition of the spontaneous firing rate, the average IC50 for TAPS was calculated to be 1.9 nM, a value lower than that reported for dermorphin or morphine. The TAPS-induced effects were antagonized by naloxone, with a dissociation equilibrium constant of 1.96 +/- 0.14 nM. The results indicate that TAPS binds to mu-opioid receptors on the cell membrane of neurons of the locus coeruleus to cause its inhibitory actions. In behavioral study, TAPS was microinjected bilaterally via chronically implanted cannulae into the locus coeruleus of non-anesthetized rats and its effects on locomotor activity determined. TAPS, at concentrations of 1 microM and 10 microM, but not of 0.1 microM, induced hypolocomotion/sedation and the effect was significantly reversed by naloxone (5 mg/kg i.p.). Taken together, these data suggest that TAPS has an inhibitory effect on neurons of the locus coeruleus and produces hypolocomotive/sedative effects in vivo.

Analgesics↗