Biomedical subjects

Y Shen

Publications and source records attributed to Y Shen.

At least 289 records · Page 16Linked to original sources

PubMed1998

A human carcinoma model in athymic rats reflecting solid and disseminated colorectal metastases.

We studied the metastatic properties of human tumor cells and tumor cell dissemination in a xenograft tumor model for human colorectal carcinoma in athymic rats which shows a reproducible pattern of metastases similar to the clinical situation. Such a model is also attractive for evaluating several therapeutic approaches. The tumor cell lines HT-29 and WiDr which are derived from the same colorectal tumor and exhibit a similar tumorigenic potential after subcutaneous injection were injected into the portal venous system of 4-week-old male nude rats. After injection of WiDr cells no liver metastases were observed; however, 50% of the rats developed liver metastases 4-12 weeks after injection of HT-29. Immunostaining of the liver cryosections at different times after injection revealed a total disappearance of WiDr cells within the first 12 h. A subpopulation of HT-29 (HT29-b) with increased metastatic activity was isolated by double selection and recultivation of cells from induced liver metastases. After a 6- to 12-week period rats injected with HT-29b showed a pattern of metastases with additional lung metastases and in some cases peritoneal carcinosis. In addition to immunohistochemistry cytokeratin 20 reverse transcriptase-polymerase chain reaction was confirmed to be a sensitive and specific tool for the detection of disseminated tumor cells in different compartments.

Animals↗

PubMed1998

Inhibin and ovarian cancer.

Previous observations from our laboratory have demonstrated that the levels of immunoreactive inhibin (ir-inh) are elevated in almost all patients with granulosa cell tumours and in the majority of postmenopausal women with mucinous ovarian cancers. The present manuscript confirms these findings in a larger group of postmenopausal women. Immunohistochemistry for the inhibin alpha, betaA and betaB subunits shows predominantly epithelial staining in granulosa cell tumours and in the majority of mucinous cancers. Serous cystadenocarcinomas also frequently show positive staining. Studies seeking to identify G alpha(i-2) or FSH receptor mutations have provided negative results in contrast to other reports. Further studies of the roles of the inhibin-related family of peptides in ovarian cancer diagnosis and monitoring are clearly indicated.

Aged↗

PubMed1998

Desensitization of AMPA receptors on horizontal cells isolated from crucian carp retina.

In horizontal cells freshly dissociated from crucian carp (Carassius auratus) retina, we recorded the whole-cell responses to rapid application of glutamate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate. Currents induced by glutamate and AMPA, but not by kainate, usually showed extremely rapid desensitization. 1-(4-aminophenyl)-3-methylcarbamyl- 4-methyl-7,8-methylenedioxy-3,4-dihydro-5H-2,3-benzodiazepine (GYKI 53655), a selective AMPA receptor antagonist, was found to completely block glutamate- and kainate-induced currents, which were supposed to be mediated by activation of AMPA receptors. We further extensively studied the kinetics of desensitization of glutamate- and AMPA-induced currents in horizontal cells. The time constants for decay of whole-cell currents induced by glutamate and AMPA were 1.9 and 1.4 ms, respectively, and the equilibrium responses to glutamate and AMPA at concentrations over 1 mM were invariably less than 10% of the corresponding peak responses. We have determined the values of EC50 for glutamate and AMPA as 1.08 and 1.05 mM, respectively, which are nearly 100-fold higher than that reported previously. Dose dependence of desensitization was also investigated and the glutamate concentration for a half desensitization was 26 microM, much lower than the EC50. Furthermore, kainate and AMPA interacted at AMPA receptors of horizontal cells in a dual competitive manner: the response to kainate of low concentration (10 microM) was potentiated by the addition of 300 microM AMPA, while the responses induced by kainate of relatively higher doses (300 microM or more) were reduced. We conclude that crucian carp horizontal cells may exclusively express the AMPA subtype of glutamate receptors, which is characterized by extremely rapid desensitization.

Animals↗

PubMed1998

Expressing mRNAs for presenilin-1 and amyloid precursor protein (APP-695) from same neuronal populations in rat hippocampus.

Presenilin-1 gene (PS1, s182) encoding a protein that contains seven transmembrane domains was recently identified as a risk factor for Alzheimer's disease (AD). Mutations on this gene may contribute to pathogenesis of AD. In this study, we used in situ hybridization histochemistry to detect the expression of PS1 in neurons in the hippocampal formation and cerebral cortex of the rat brain. Specifically, mRNAs of PS1 were predominantly found in pyramidal neurons in CA1, CA3, and granule cells in the hilar region of the dentate gyrus of the hippocampus and in the external and internal pyramidal layers of the cerebral cortex. The same neuronal populations express the amyloid protein precursor (APP-695). Transgenic mice expressing a mutated APP-695 produced increased levels of beta-amyloid (A beta) and exhibited behavioral deficits. These results lead us to suggest that when PS1 and APP-695 colocalize in neurons in the brain, PS1 may play a regulatory role in production of (A beta) protein of AD.

Amyloid beta-Protein Precursor↗

PubMed1998

Specific bone-protective effects of metabolites/derivatives of tamoxifen and clomiphene in ovariectomized rats.

In the ovariectomized (ovx) rat, the nonsteroidal antiestrogens, clomiphene (CLO) and tamoxifen (TAM), at dose levels that prevent development of osteopenia to a degree approaching that of 17beta-estradiol are, in contrast to 17beta-estradiol, only weakly uterotrophic. Metabolites of CLO and TAM might contribute differentially to these effects. Thus, we have evaluated bone protective and uterine effects in ovx rats of two such metabolites: 4-hydroxy CLO, produced by p-hydroxylation of CLO; and 4HTA, produced from TAM by stepwise replacement of its dimethylaminoethyl side chain with an acetic acid moiety, accompanied by p-hydroxylation. Also reported are effects of D4HTA, the dihydrodesethyl derivative of 4HTA previously characterized as a full estrogen mimetic in vitro. Administration of 4-hydroxy CLO (2.5 mg/kg subcutaneously) 5 days/week for 5 weeks to 3-month-old ovx rats resulted in complete prevention of bone loss and suppression of bone turnover to levels comparable to those of intact controls and to those of ovx animals similarly receiving 17beta-estradiol (10 microg/kg). However, uterine weight in animals receiving 4-hydroxy CLO was 64% less than that in 17beta-estradiol-treated animals. Although 4HTA (3.7 mg/kg s.c.) had a modest uterotrophic effect, it did not prevent bone loss associated with ovariectomy. In contrast, D4HTA (3.6 mg/kg s.c.) partially reduced bone turnover indicators and cancellous bone loss in a manner similar in many ways to that observed in TAM-treated ovx animals, but it had no uterotrophic effect. These results suggest that, although 4HTA does not contribute to the bone-protective effect of TAM, 4-hydroxy CLO might augment that of CLO.

Animals↗

PubMed1998

Genetic relationships within the genus Beta determined using both PCR-based marker and DNA sequencing techniques.

The sequences of ITS1 of the internal transcribed spacer regions of nuclear ribosomal DNA from 11 species or subspecies in four sections of the genus Beta were compared. Phylogeny of these wild beet taxa was inferred from the sequence data using phenetic and phylogenetic analyses. Multiple accessions from the same 11 taxa were subjected to random amplified polymorphic DNA (RAPD) analysis, and the data were analysed phenetically. With both molecular techniques and each analysis, three distinctive groups were formed: species from section Beta formed one group; species from section Procumbentes formed a very distinct group; and species from both section Nanae and section Corollinae clustered together forming the third group, which is closer to Beta than Procumbentes. The RAPD data revealed within-section interspecies relationships that are consistent with those reported previously; this was not always the case using the single-locus sequence data.

Base Sequence↗

PubMed1998

Neurovascular supply of the gracilis muscle: a study in the monkey and human.

A comparison of the gross anatomy, extramuscular nerve branches, and intramuscular blood supply of the gracilis muscle showed similar patterns in both monkey and human. The number and pattern of distribution of the extramuscular terminal branches to the muscle were similar. The intramuscular neural pattern demonstrated with the Sihler's staining technique was also similar in both species. In vivo electrical stimulation studies in the monkey revealed that stimulating each extramuscular terminal nerve branch produced a distinct segmental contraction of the muscle. Independent contraction with force generation was observed when the monkey muscle was split into anterior and posterior segments and stimulated through each of the two subdivisions of the main nerve trunk to the muscle. Angiograms verified that circulation was preserved in these two segments.

Animals↗

PubMed1998

Helical CT reconstruction with longitudinal filtration.

Each of the currently used helical reconstruction algorithms represents one tradeoff selection of the image noise or mA requirement and resultant artifacts versus the width of the section profile. For many applications, the performance tradeoffs different from those existed are desired. In this paper, we present a general framework of incorporating the longitudinal (z) filtration in helical CT reconstruction, which leads to a new class of helical reconstruction algorithms with tunable performance characteristics to suit various applications. The z-filtering algorithm enables us to derive the performance curve of image noise or mA requirement versus the width of the section profile, whereas the existing helical reconstruction algorithms only represent limited discrete samples of the curve. We demonstrate that using a new helical reconstruction algorithm derived from this general framework, a substantial reduction in image noise or mA requirement can be achieved with a slight increase of FWHM of the section profile. Thus for many applications requiring both compact section profile and low image noise or mA requirement, the new algorithm represents a better tradeoff than both the 180 degrees and 360 degrees interpolation algorithms. The new algorithm also offers the following potential clinical benefits: (1) longer x-ray tube life; (2) longer scan duration with less x-ray tube cooling delays--longer volume coverage and/or longer thin-slice scan; (3) less radiation to patient; (4) less image noise; and (5) less helical artifacts. Initial clinical results are also presented.

Abdomen↗

PubMed1998

Identification of hydrocarbon-degrading bacteria in soil by reverse sample genome probing.

Bacteria with limited genomic cross-hybridization were isolated from soil contaminated with C5+, a mixture of hydrocarbons, and identified by partial 16S rRNA sequencing. Filters containing denatured genomic DNAs were used in a reverse sample genome probe (RSGP) procedure for analysis of the effect of an easily degradable compound (toluene) and a highly recalcitrant compound (dicyclopentadiene [DCPD]) on community composition. Hybridization with labeled total-community DNA isolated from soil exposed to toluene indicated enrichment of several Pseudomonas spp., which were subsequently found to be capable of toluene mineralization. Hybridization with labeled total-community DNA isolated from soil exposed to DCPD indicated enrichment of a Pseudomonas sp. or a Sphingomonas sp. These two bacteria appeared capable of producing oxygenated DCPD derivatives in the soil environment, but mineralization could not be shown. These results demonstrate that bacteria, which metabolize degradable or recalcitrant hydrocarbons, can be identified by the RSGP procedure.

Journal Article↗

PubMed1998

Polymerase (Pol) III TATA box-binding protein (TBP)-associated factor Brf binds to a surface on TBP also required for activated Pol II transcription.

The TATA box-binding protein (TBP) plays an essential role in transcription by all three eukaryotic nuclear RNA polymerases, polymerases (Pol) I, II, and III. In each case, TBP interacts with class-specific TBP-associated factors (TAFs) to form class-specific transcription initiation factors. For yeast Pol III transcription, TBP associates with Brf (from TFIIB-related factor) and B", two Pol III TAFs, to form Pol III transcription factor TFIIIB. Here, we identify TBP surface residues that are required for interaction with yeast Pol III TAFs. Ninety-one human TBP surface residue mutants with radical substitutions were analyzed for the ability to form stable gel shift complexes with purified Brf and B" and for their activities for in vitro synthesis of yeast U6 snRNA. Mutations in a large positively charged epitope extending from the top (that is, on the surface opposite the DNA-facing "saddle" of TBP) and onto the side of the first TBP repeat inhibited binding to Brf (residues K181, L185, R186, E206, R231, L232, R235, K236, R239, Q242, K243, K249, and F250). A triple-mutant TBP (R231E + R235E + R239S) had greatly reduced activity for yeast U6 snRNA gene transcription while remaining active for Pol II basal transcription. Similar results were observed when selected mutations were introduced into yeast TBP at equivalent positions. A C-terminal fragment of Brf lacking the region of homology with TFIIB retains the ability to bind TBP-DNA complexes (G. Kassavetis, C. Bardeleben, A. Kumar, E. Ramirez, and E. P. Geiduschek, Mol. Cell. Biol. 17:5299-5306, 1997); the same TBP mutations reduced binding by this fragment. Mutations in TBP residues that interact with TFIIB did not affect Brf binding or U6 gene transcription. These results indicate that Brf and TFIIB interact differently with TBP. An extensively overlapping epitope on the top surface of TBP was found previously to be required for activated Pol II transcription and has been hypothesized to interact with Pol II TAFs. Our results map the surface of TBP that interacts with Brf and suggest that Pol II and Pol III TAFs interact with the same surface of TBP.

DNA-Binding Proteins↗

PubMed1998

Endotoxin-induced migration of monocytes and PECAM-1 phosphorylation are abrogated by PAF receptor antagonists.

The trafficking of monocytes across the endothelial lining of the blood vessel increases in response to bacterial infection at sites of inflammation. However, the molecular events involved in the diapedesis of monocytes in response to endotoxin are not completely understood. Our studies revealed that signaling by lipopolysaccharide (LPS) in human umbilical vein endothelial cells (HUVEC) resulted in a threefold increase in the transendothelial migration of monocyte-like HL-60 cells and a sevenfold increase in the phosphorylation of platelet endothelial cell adhesion molecule-1 (PECAM-1). The transmigration induced by LPS was inhibited by an antibody to PECAM-1. Both the phosphorylation of PECAM-1 and transendothelial migration of monocytes were inhibited by a platelet-activating factor (PAF) receptor antagonist, indicating the autocrine effect of PAF in these events. Treatment of HUVEC with LPS caused a fourfold increase in PAF receptor mRNA expression that was completely blocked by the PAF receptor antagonist. We conclude that PAF, generated by HUVEC in response to LPS or gram-negative bacterial infection, acts in an autocrine manner, causing PECAM-1 phosphorylation and thus the transendothelial migration of monocytes.

Azepines↗

PubMed1998

Lack of effect of spaceflight on bone mass and bone formation in group-housed rats.

As part of an experiment to study the role of corticosteroids in bone changes during spaceflight, male Sprague-Dawley rats (6 wk old, 165 g body weight) were placed in orbit for 17 days, in groups of six, in animal-enclosure modules (AEMs) aboard the space shuttle Columbia (STS-78). Control rats were group housed in a similar manner in ground-based AEMs or standard vivarium cages. Adrenal hypertrophy occurred in flight rats, but bone histomorphometric analyses revealed a lack of significant changes in bone mass and bone formation in these animals. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were nearly the same in flight and ground-based rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral necks of flight rats. In the tibial diaphysis, periosteal bone formation rate was found to be identical in flight and ground-based rats. The results indicate that, under conditions of group housing in AEMs, spaceflight has minimal effects on bone mass and bone formation in rapidly growing rats. These findings emphasize the need to investigate the importance of rat age, strain, and especially housing conditions for studies of the skeletal effects of spaceflight.

Adrenal Cortex Hormones↗

PubMed1998

Bopindolol: a slowly dissociating antagonist from the beta-adrenoceptors in guinea pig atria.

The dissociating and/or residual inhibitory effects of bopindolol from beta-adrenoceptors of atria strips pretreated with this drug which was then washed out with buffers on the responses to isoprenaline were determined and compared with those of propranolol, pindolol, atenolol, and the two active metabolites of bopindolol: 18-502 and 20-785. Low concentrations of bopindolol (10(-9) to 10(-8) mol/l) and the active metabolite 18-502 (10(-9) mol/l) produced rightward shifts of the concentration-response curves. On the other hand, high concentrations of bopindolol (10(-7) mol/l) and metabolite 18-502 (10(-8) and 10(-7) mol/l) produced a reduced maximum response by isoprenaline, suggesting that these nonparallel rightward shifts have pD2 values of 7.57 (bopindolol) and 7.67 (18-502), respectively, at 0 min after washout with buffers. Pindolol (10(-7) mol/l) and propranolol (10(-7) and 10(-8) mol/l) also produced a rightward shift of isoprenaline response curves, and these concentration-response curves in guinea pig atria strips pretreated with pindolol (10(-7) mol/l) and propranolol (10(-6) mol/l) recovered to control levels. Neither of these drugs, however, reduced the maximum response by isoprenaline. A high concentration (10(-5) mol/l) of atenolol was required for a rightward shift of the isoprenaline concentration-response curve, and this drug also did not reduce the maximum response. Thus, we conclude that bopindolol and metabolite 18-502 slowly dissociate and act as noncompetitive beta-antagonists rather than easily reversible beta-adrenoceptor antagonists.

Adrenergic beta-Agonists↗

PubMed1998

No evidence of a role for mutations or polymorphisms of the follicle-stimulating hormone receptor in ovarian granulosa cell tumors.

The molecular pathogenesis of granulosa cell tumors of the ovary is not understood, although recent studies have shown that immunoreactive inhibin secretion by these tumors may be used as a tumor marker. Granulosa cell tumors exhibit many features of normal granulosa cells, including a response to FSH and inhibin secretion. FSH levels are suppressed in patients with inhibin-secreting granulosa cell tumors, suggesting FSH-independent growth of these tumors. Activating mutations of the FSH receptor might, therefore, be involved in tumorigenesis. We sought to identify mutations in the FSH receptor genes of these tumors using PCR to amplify the exon encoding the transmembrane and cytoplasmic domains from the tumor DNA. Analysis of the amplicons for single strand conformational polymorphisms and direct sequencing confirmed a previously reported polymorphism in the C-terminal region of the receptor, but did not identify tumor-specific missense mutations and/or polymorphisms. In addition, ribonucleic acid from 3 granulosa cell tumors was used to confirm expression of the FSH receptor; expression was unexpectedly also observed in several ovarian mucinous cystadenocarcinomas used as controls. In conclusion, our failure to identify activating mutations of the FSH receptor in 15 granulosa cell tumors argues against a role for the FSH receptor in tumorigenesis and suggests that some subsequent component of this signal transduction pathway may be activated.

Alleles↗

PubMed1998

Microcystic cyanobacteria causes mitochondrial membrane potential alteration and reactive oxygen species formation in primary cultured rat hepatocytes.

Cyanobacteria contamination of water has become a growing public health problem worldwide. Microcystis aeruginosa is one of the most common toxic cyanobacteria. It is capable of producing microcystins, a group of cyclic heptapeptide compounds with potent hepatotoxicity and tumor promotion activity. The present study investigated the effect of microcystic cyanobacteria on primary cultured rat hepatocytes by examining mitochondrial membrane potential (MMP) changes and intracellular reactive oxygen species (ROS) formation in cells treated with lyophilized freshwater microcystic cyanobacteria extract (MCE). Rhodamine 123 (Rh-123) was used as a fluorescent probe for changes in mitochondrial fluorescence intensity. The mitochondrial Rh-123 fluorescence intensity in MCE-treated hepatocytes, examined using a laser confocal microscope, responded in a dose- and time-dependent manner. The results thus indicate that the alteration of MMP might be an important event in the hepatotoxicity caused by cyanobacteria. Moreover, the parallel increase of ROS formation detected using another fluorescent probe, 2',7'-dichlorofluorescin diacetate also suggests the involvement of oxidative stress in the hepatotoxicity caused by cyanobacteria. The fact that MMP changes precede other cytotoxic parameters such as nuclear staining by propidium iodide and cell morphological changes suggests that mitochondrial damage is closely associated with MCE-induced cell injury in cultured rat hepatocytes.

Animals↗

PubMed1998

An evaluation of ruminally degradable intake protein and metabolizable amino acid requirements of feedlot calves.

Ruminally degradable intake protein (DIP) and metabolizable indispensable amino acid (MIAA) requirements of feedlot steers were evaluated. Dietary treatments consisted of isocaloric 80% concentrate steam-flaked corn-based diets containing either .8% urea, 1.5% fish meal (FM), 3.0% FM, 4.5% FM, or 4.5% soybean meal (SBM). Treatment effects on characteristics of ruminal and total tract digestion were evaluated using four Holstein steers (249 kg) with cannulas in the rumen and proximal duodenum. Ruminal digestibility of OM (RDOM; P < .05) and feed N (P < .01) and microbial N flow (MNF; P < .01) to the small intestine were greater with urea as the supplemental N source. The level of DIP was closely associated (R2 = .89) with MNF. Postruminal digestibility of OM was greater (P < .05) for FM than for urea-supplemented diets, compensating for lower RDOM. There were no treatment effects (P > .10) on DOM. As the level of FM was increased, MIAA increased linearly (P < .01). Intestinal MIAA were similar (P > .10) for urea- and SBM-supplemented diets. Treatment effects on 56-d growth performance were evaluated using 100 medium-framed crossbred steers (231 kg). Daily weight gain (linear effect; P < .01), DM intake (linear effect; P < .10), feed efficiency (linear effect; P < .05), and diet NE (linear effect; P < .05) increased with level of FM supplementation. Daily weight gain (P < .10) and DM intake (P < .05) were greater for urea- than for SBM-supplemented diets. Using bovine tissue as the reference protein, the biological value (based on chemical score) of the intestinal chyme protein averaged 73%; methionine was first-limiting. There was a close association (R2 = .99) between methionine supply to the small intestine and observed/expected dietary NE. The metabolizable methionine requirement (MMETR, g/d) of medium-framed feedlot steers can be reliably predicted from measures of BW and ADG (MMETR = 1.565 + .0234ADG[268 - (29.4 x .0557BW(.75)ADG(1.097))/ADG] + .0896BW(.75)). There was a very close association (R2 = .89) between DIP and MNF (MNF = 13.7DIP - .66DIP(2) + 25.9). At maximal observed synthesis, DIP accounted for 76% of the MNF. A minimum of 100 g DIP/kg of total tract digestible OM was required to maximize RDOM and MNF.

Amino Acids↗

PubMed1998

Influence of dietary magnesium level on growth-performance and metabolic responses of Holstein steers to laidlomycin propionate.

We used 216 Holstein steers (151 kg) in a 262-d trial to evaluate the influence of dietary magnesium level (.19, .25, and .32%) and laidlomycin propionate (LP; 0 vs 11 ppm, air-dry basis) on growth performance and NE value of the diet. During the initial 112 d of the trial, LP increased (P < .01) ADG (6.3%) and feed efficiency (4.2%). From d 112 until slaughter, LP increased (P < .05) ADG (9.7%) and feed efficiency (4.5%). Across the 262-d feeding period, LP supplementation enhanced (P < .01) ADG (8.9%) and feed efficiency (6.3%). There was an interaction (P < .05) between dietary Mg and LP on NE value of the diet. The enhancement in NE value of the diets owing to LP with .19, .25, and .32% dietary Mg were .5, 3.0, and 5.9%, respectively. Six Holstein steers (302 kg) were used in a 6 x 6 Latin square experiment to evaluate treatment effects on characteristics of ruminal and total tract digestion. There were no treatment interactions (P > .10) on site and extent of digestion of OM, starch, and N. Supplemental Mg increased (quadratic effect, P < .10) ruminal OM digestion. Neither LP nor dietary Mg level affected (P > .10) ruminal digestion of starch and feed N. Supplemental LP decreased (15%, P < .05) ruminal microbial efficiency. Total tract digestion of OM and N increased (linear effect, P < .01) with increasing dietary Mg level. There were interactions between LP and dietary Mg level on ruminal soluble-Mg concentration (linear effect, P < .01) and Mg absorption (quadratic effect, P < .05). Apparent total tract Mg digestion increased owing to LP (P < .01) and dietary Mg level (linear effect, P < .01). There were no treatment effects (P > .10) on ruminal pH. Dietary Mg level did not influence (P > .10) ruminal VFA concentrations or molar proportions. Supplemental LP increased (14%; P < .10) total ruminal VFA concentration but did not affect (P > .10) VFA molar proportions. We conclude that LP will increase daily weight gain and feed efficiency of calf-fed Holstein steers and that this response may be enhanced by increasing dietary Mg level.

Adipose Tissue↗

PubMed1998

[Decrease of cAMP and increase of amino acids contents in mouse brain after dihydroetorphine tolerance].

AIM: To study the mechanism of dihydroetorphine (DHE) tolerance. METHODS: DHE tolerance was produced by repeated s.c. injections in progressively increased doses to mice for 8 d. The concentrations of amino acids and cAMP were detected by RP-HPLC/fluorescence assay and radioimmunoassay, respectively. RESULTS: The basal contents of glutamic acid (Glu), aspartic acid (Asp), and GABA in whole brain (cerebellum removed) were increased respectively from 14.1 +/- 2.1, 3.0 +/- 0.4, and 1.8 +/- 0.8 mumol/g tissue in control mice to 17.2 +/- 2.2, 4.1 +/- 0.6, and 3.2 +/- 1.0 mumol/g tissue in tolerant mice, and the rates of increase were 22.0% (P < 0.05), 36.7% (P < 0.01), and 77.8% (P < 0.05 vs control), respectively. There was no significant difference in the basal contents of Gln (5.1 +/- 1.0 vs 4.5 +/- 1.7 mumol/g tissue of control). The basal contents of cAMP in hypothalamus and striatum were decreased respectively from 271 +/- 38 and 189 +/- 31 nmol/g tissue in control mice to 96 +/- 15 and 65 +/- 21 nmol/g tissue in tolerant mice (P < 0.01), and the rates of decrease were 64.6% and 65.6%, respectively. There was no significant difference of cAMP in cerebral cortex (72 +/- 20 vs 55 +/- 15 nmol/g tissue of control). CONCLUSION: The increases of Glu, Asp, and GABA in brain and the decrease of cAMP in hypothalamus and striatum were involved in DHE tolerance.

Amino Acids↗