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11.
Ethanol Feeding Causes Inactivation of Both State 1 and State 2 Rat Hepatic Asialoglycoprotein Receptors 总被引:1,自引:0,他引:1
Benita L. Tworek Janet A. Oka Carol A. Casey Paul H. Weigel 《Alcoholism, clinical and experimental research》1997,21(8):1429-1434
Previous studies have shown that ethanol feeding in rats causes inactivation and redistribution of ˜50% of the total asialoglycoprotein receptors (ASGPRs) in hepatocytes (Tworek et al., J. Biol. Chem. 271:2531, 1996), and that two equal populations of hepatic ASGPRs mediate ligand uptake and processing via two functionally different pathways (Weigel in Glycoconjugates: Composition, Structure and Function , Marcel Dekker, 1992, p. 421). The purpose of this study was to determine if ethanol feeding causes preferential inactivation of only one of these two ASGPR populations, which have been designated state 1 and state 2 ASGPRs. The state 2, but not state 1, ASGPRs are inactivated in isolated hepatocytes by a variety of drugs and inhibitors. State 2 ASGPRs can also be inactivated in permeable cells by ATP treatment and then reactivated by treatment with fatty acyl coenzyme As. In the present study, permeable cell assays for state 2 ASGPR inactivation and reactivation were used to assess whether hepatocytes from ethanol-fed rats contain inactive state 2 ASGPRs. The results show that preferential inactivation of one ASGPR population does not occur after ethanol feeding. That inactive ASGPRs could not be reactivated by treatment with palmitoyl-coenzyme A to a greater extent in ethanol-fed versus control cells indicates there is not a larger pool of inactivated state 2 ASGPRs in treated cells. We conclude that ethanol feeding causes equal inactivation of both state 1 and state 2 ASGPRs. Ethanol feeding may represent the first treatment found to inactivate state 1 ASGPRs. 相似文献
12.
Joseph R. Ghilardi Clark J. Allen Steven R. Vigna Douglas C. McVey Patrick W. Mantyh 《Brain research》1994,633(1-2)
A [125I]cholecystokinin (CCK) analog and [125I]peptide YY (PYY) were used to localize and characterize CCK and neuropeptide Y (NPY) receptor binding sites in the rabbit vagal afferent (nodose) ganglion. High concentrations of CCK and NPY binding sites were observed in 10.6% and 9.2% of the nodose ganglion neurons, respectively. Pharmacological experiments using CCK or NPY analogs suggest that both subtypes of CCK (CCK-A and CCK-B) and NPY (Y1 and Y2) receptor binding sites are expressed by discrete populations of neurons in the nodose ganglion. These results suggest sites at which CCK or NPY, released in either the nucleus of the solitary tract or a peripheral tissue, may modulate the release of neurotransmitters from a select population of visceral primary afferent neurons. Possible functions mediated by these receptors include modulation of satiety, opiate analgesia, and the development of morphine tolerance. 相似文献
13.
采用石蜡切片免疫组化法,测定了48例胃癌组织中雌激素受体的分布。结果阳性者17例,阳性率35.4%;同时测定12例非肿瘤性胃粘膜(慢性炎症及胃溃疡)作为对照,结果仅1例阳性(8.3%),两者之间有明显差异(P<0.01)。各年龄组及性别间差异均无统计学意义。将胃癌分成分化型及未分化型(包括印戒细胞癌)两组,结果显示未分化型癌的阳性率(61.5%)比分化型者(18.2%)明显增高(P<0.0l)。表示雌激素在癌的发生、发展中有明显的刺激作用,癌细胞的生长及恶性度对雌激素有一定依赖性。临床上应用内分泌疗法对雌激素受体阳性肿瘤进行辅助治疗是行之有效的。 相似文献
14.
Novel multi-probe RNase protection assay set for detection of endotoxin associated receptors gene expression 总被引:2,自引:0,他引:2
Objective: To construct the multi-probe ribonuclease protection assay (RPA) template set to be used for detecting expression patterns of MD-2, TLR4, CD14 mRNAs in human peripheral blood mononuclear cells. Methods : The designed cDNA fragments of the three genes were generated by polymerase chain reaction (PCR)using specific primers and directionally cloned into EcoR I and Hind III sites of expression plasmid pSP72 containing the T7/ promoter, the linearized plasmids was used as template to synthesize anti-sense RNA probes. Then we extracted total RNA from peripheral blood mononuclear cells (PBMC) and detected the dynamic expression patterns of the three genes with RPA method. Results: The proper sequence and orientation of the template set were confirmed by sequencing and the template set was successfully used to assay TLR4, MD-2 and CD14 mRNAs in human PBMC. The results showed that the three detected genes decreased transiently 1-3 hours after 100 ng/ml LPS stimulation. Conclusions: These new RPA multi-probe set provided valuable tool for the simultaneous quantitative determination of expression of TLR4, CD14 and MD-2 mRNAs in both constitutive and inducible types. 相似文献
15.
David Mischoulon Darin D. Dougherty Kathryn A. Bottonari Robert L. Gresham Shamsah B. Sonawalla Alan J. Fischman Maurizio Fava 《Psychiatry Research: Neuroimaging》2002,116(3):151-161
Nefazodone has been widely used as an antidepressant, but it has not been tested for depression with anger attacks. In an open study, we administered nefazodone (maximum 600 mg/day) for 12 weeks to 16 outpatients who had major depression with anger attacks. Assessment instruments comprised the Structured Clinical Interview for DSM-IV (SCID), Anger Attacks Questionnaire (AAQ), 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinician Global Impression Scale (CGI), Symptom Questionnaire (SQ), Modified Overt Aggression Scale (MOAS), and MOAS-Self-Rated. Three subjects underwent positron emission tomography (PET) with [18F]-setoperone for 5-HT2 binding potential (BP) and [11C]-SCH-23,390 for D1 BP, both at baseline and after 6 weeks of treatment. Eight subjects underwent PET with [18F]-setoperone and with [11C]-SCH-23,390 at baseline only. In an examination of whether D1 and 5HT2 (data available in six subjects) receptor BP predicted treatment response, we found significant decreases in the HAM-D-17, CGI-S, weighted MOAS, MOAS verbal scale, OAS Self-Rated verbal, SQ Depression and Anger/Hostility scales after nefazodone; 50% responded to nefazodone (defined as ≥50% decrease in HAM-D-17 score), and 44% reported disappearance of anger attacks. A statistically significant percentage decrease in 5HT2 BP was observed for the right mesial frontal and left parietal regions after 6 weeks of treatment. No significant change was observed in D1 BP in any region. Although CGI-I scores correlated significantly with D1 BP in the left thalamic region, the correlation was not significant after Bonferroni correction. The effectiveness of nefazodone for depression with anger attacks may be related to widespread changes in 5HT2 receptor BP. 相似文献
16.
The presence and binding properties of epidermal growth-factor receptors (EGF-Rs) in different cell types purified from the rat medial septal area in culture were investigated. We report that astrocytes, oligodendrocytes and neurons from this area possess EGF-Rs while microglia do not. EGF-binding sites are detectable on astrocytes derived from the medial septum of both embryonic and neonatal rats. Scatchard analysis of the data for astrocytes from the fetal rats show that EGF specifically binds to both high- (Kd = 7.21 × 10−10 M, Bmax = 3602 receptors/cell) and low-affinity (Kd = 3.99 × 10−8 10−8 M, Bmax = 6,265 receptors/cell) receptors on these cells. On the other hand, astrocytes purified from neonatal tissue possess a greater number of high-affinity receptors (Bmax = 10,938 receptors/cell) when compared with the embryonic astroglia. With time in culture, the number of both types of receptors on neonatal astrocytes decreases. Oligodendrocytes also possess high- and low-affinity EGF-Rs with dissociation constants of 3.25 × 10−10 M and 3.85 × 10−8 M, respectively. The number of receptors on oligodendrocytes is significantly lower than those on neonatal astrocytes (Bmax = 1185 and 25,081 receptors/cell for high- and low-affinity binding sites, respectively). Finally, neurons from this area also exhibit two different EGF-R types with dissociation constants similar to those described for astrocytes. As the number of receptors/neuron (Bmax = 136 and 1159 receptors/cell for high- and low-affinity binding sites, respectively) appears to be extremely low, it is possible that EGF specifically binds only to a subpopulation of neurons from this area. These studies demonstrate which cell types in the developing medial sepal area posses EGF-Rs and provide a detailed characterization of these binding sites. These EGF-R-bearing cells may be potential targets for this growth factor or for transforming growth factor α in this brain area. 相似文献
17.
Differential effects of substance P on serotonin-modulated spinal nociceptive reflexes 总被引:2,自引:0,他引:2
Recent immunohistochemical studies indicate the presence of a bulbospinal substance P (SP) system, as well as a bulbospinal
serotonin (5-HT) system, involved in spinal pain transmission. Although electrophysiological studies indicate that SP may
modulate the effects of 5-HT on post-synaptic spinal nociceptive neurons, the functional relationship between SP and 5-HT
on “pain behavior” remains obscure. To bridge this gap between mechanism and behavior, the purpose of the present study was
to determine specific postsynaptic behavioral effects of SP and 5-HT on local spinal nociceptive reflexes in spinally transected
animals. Administration of the 5-HT agonists 5-methoxydi-methyltryptamine (5-MeODMT) (0, 0.5, 1.5, 2.0 mg/kg) and quipazine
(0, 5, 10, 20 mg/kg) 2 days after transection significantly expanded the receptive field (RF) areas of three spinal reflexes,
as previously reported. Intrathecal administration of SP alone (0, 0.25, 2.5, 7.5 ng) also resulted in hyperalgesia, indicated
by a significant expansion of the RF areas of all three nociceptive reflexes. However, administration of SP, in animals pretreated
with 5-HT agonists, decreased the 5-HT-induced expansion of RF size. Therefore, SP had opposite effects on spinal nociceptive
reflexes depending on whether or not the animal was pretreated with 5-HT agonists, i.e., hyperalgesia in the absence of 5-HT
agonists, and analgesia in the presence of 5-HT agonists. The two effects of SP on local spinal reflexes may be related to
the anatomical organization of the two spinal SP systems: 1) SP released from primary afferents facilitates nociceptive reflexes,
and 2) SP associated with the descending bulbospinal system interacts with the descending bulbospinal 5-HT system and inhibits
nociceptive reflexes. The present results help explain contradictory literature regarding the effect of SP on spinal nociceptive
reflexes. 相似文献
18.
The steady-state density and the turnover rates of D1-dopamine receptors were investigated in the striatum, nucleus accumbens, substantia nigra, and retina of adult (3-month-old) and aged (23-month-old) rats. The turnover rates were measured by monitoring the repopulation kinetics of D1-dopamine receptors labeled with [3H]-SCH 23390 after the irreversible inactivation induced by a single dose of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 10 mg/kg, s.c.). In all the neural tissues examined, the repopulation of D1 dopamine receptors could be adequately described by a theoretical model that assumes a constant rate of receptor production (i.e. zero order) and a rate of degradation that is dependent on the receptor density at any time (i.e. first order). The results obtained indicate that the reduction in the density of D1-dopamine receptors in the striatum, nucleus accumbens and substantia nigra of aged rats is the result of a larger decrease in the receptor production rate (−44 to −60%) than in the receptor degradation rate (−21 to −46%). By contrast, the production rate of D1-dopamine receptors in the retina of aged rats remains unchanged, whilst the degradation rate is reduced by 25%. This results in an age-related increase in the density of D1-dopamine receptors in the rat retina. 相似文献
19.
以125Ⅰ-LDL为配体对食管癌、胃癌及其相应的正常组织进行了LDL受体水平的测定,同时分析了各组织中蛋白质、DNA的含量,以探讨食管癌和胃癌发生与LDL代谢之间的关系。结果显示,癌组织和正常组织的LDL受体亲和性差异无显著性,但癌变组织的蛋白质、DNA和LDL受体水平均明显高于相应正常组织。癌细胞需要大量的胆固醇满足其有丝分裂,细胞通过受体升高机制使LDLR增多,以增加对LDL的摄取和利用。 相似文献
20.
Hideaki Ban Hiroyuki Kato Tsutomu Araki Hideaki Fujikura Yoshinari Hasegawa Kyuya Kogure 《Brain research》1994,646(2)
We investigated the effects of age and naftidrofuryl oxalate (Naftidrofuryl), a 5-HT2 antagonist, on neurotransmission and transduction systems in the gerbil hippocampus using quantitative autoradiography. [3H]Quinuclidinyl benzilate (QNB), [3H]cyclohexyl-adenosine (CHA), [3H]MK-801, and [3H]muscimol were used to label muscarinic acetylcholine, adenosine A1, N-methyl-d-aspartate (NMDA), and γ-aminobutyric acid-A (GABAA) receptors, respectively. [3H]PN200-110 labeled L-type Ca2+ channels. [3H]Forskolin, [3H]cyclic adenosine monophosphate (cAMP), [3H]phorbol 12,13-dibutyrate (PDBu), and [3H]inositol 1,4,5-triphosphate (IP3) were used to label adenylate cyclase, cAMP-dependent protein kinase, protein kinase C (PKC), and IP3 receptors, respectively. Approximately 20% reductions in [3H]QNB, [3H]forskolin, and [3H]PDBu binding were observed in the hippocampus of 9-month-old gerbils in comparison with 5-week-old gerbils. Treatment with Naftidrofuryl (10 mg/kg, i.p., once a day for 7 days) ameliorated these reductions. No changes were found in [3H]CHA, [3H]MK-801, [3H]muscimol, [3H]PN200-110, [3H]cAMP, and [3H]IP3 binding. The results suggest that Naftidrofuryl may have beneficial effects on the age-related alterations in signal transmission and transduction systems in the brain. Because the acetylcholine system, adenylate cyclase, and PKC are considered to be involved in learning and memory processes, the result may have clinical implications. 相似文献