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1.
Juan F López-Giménez Laurence H Tecott José M Palacios Guadalupe Mengod M Teresa Vilaró 《Journal of neuroscience research》2002,67(1):69-85
Quantitative receptor autoradiography was used to study possible alterations of the densities of multiple serotonin (5-HT) receptor subtypes and of serotonin transporter in the brain of 5-HT(2C) receptor knockout mice. The radioligands employed were [(3)H]citalopram, [(3)H]WAY100,635, [(3)H]8-OH-DPAT, [(3)H]GR125743, [(3)H]sumatriptan, [(3)H]MDL100,907, [(125)I](+/-)DOI, [(3)H]mesulergine, [(3)H]5-HT, [(3)H]GR113808, and [(3)H]5-CT. As expected, radioligands that label 5-HT(2C) receptors showed a complete absence of labeling in mutant mice choroid plexus and significantly reduced densities in other brain regions expressing 5-HT(2C) receptors. With the rest of the radioligands, no significant alterations in the densities of labeled sites were found in any brain region. In situ hybridization showed no changes in 5-HT(2A) receptor and serotonin transporter mRNA levels, whereas 5-HT(2C) receptor mRNA levels were reduced in certain brain regions. The present results indicate that the mouse serotonergic system does not exhibit compensatory up- or down-regulation of the majority of its components (serotonin transporter and most 5-HT receptor subtypes) in response to the absence of 5-HT(2C) receptors. 相似文献
2.
Elena del Olmo Carmen del Arco Alvaro Díaz Julio Pascual Guadalupe Mengod José M. Palacios Angel Pazos 《The European journal of neuroscience》1996,8(1):53-60
The pattern of pre- and postnatal appearance of 5-HT1D receptors throughout the different areas of the human brain was studied by quantitative in vitro autoradiography, using [125 I]GTI (serotonin O -carboxymethyl-glycyl-[125 I]tyrosinamide) as a ligand. The anatomical distribution of 5-HT1D receptors in neonatal, infant and children's brain was in good agreement with that observed in the adult, the basal ganglia and substantia nigra being the most intensely labelled areas. The development of these receptors throughout the human brain was mainly postnatal: low densities of [125 I]GTI binding sites were observed at the fetal/neonatal stage in most regions analyzed, in contrast with the high levels of labelling found in infant and children's brains. Indeed, in a number of regions, including the globus pallidus, substantia nigra and visual cortex, a peak of overexpression of 5-HT1D receptors was observed in the first decade of life. Such overexpression could support a regulatory role for 5-HT1D receptors in advanced periods of the CNS developmental process. Our results also indicate that the administration of drugs acting on 5-HT1D receptors during the early postnatal period of life could result in modifications of their properties, as these receptors are already functional in this period. 相似文献
3.
Guadalupe Garrido Manuel Guzmán José M. Odriozola 《European journal of applied physiology》1996,74(1-2):91-99
Male Wistar rats were fed ad libitum four different diets containing fructose, sucrose, maltodextrins or starch as the source of carbohydrate (CH). One group was subjected to moderate physical training on a motor-driven treadmill for 10 weeks (trained rats). A second group received no training and acted as a control (sedentary rats). Glycogen metabolism was studied in the liver and skeletal muscle of these animals. In the sedentary rats, liver glycogen concentrations increased by 60%–90% with the administration of simple CH diets compared with complex CH diets, whereas skeletal muscle glycogen stores were not significantly affected by the diet. Physical training induced a marked decrease in the glycogen content in liver (20%–30% of the sedentary rats) and skeletal muscle (50%–80% of the sedentary rats) in animals fed simple (but not complex) CH diets. In liver this was accompanied by a two-fold increase of triacylglycerol concentrations. Compared with simple CH diets, complex CH feeding increased by 50%–150% glycogen synthase (GS) activity in liver, whereas only a slight increase in GS activity was observed in skeletal muscle. In all the animal groups, a direct relationship existed between tissue glucose 6-phosphate concentration and glycogen content (r = 0.9911 in liver, r = 0.7177 in skeletal muscle). In contrast, no relationship was evident between glycogen concentrations and either glycogen phosphorylase activity or adenosine 5-monophosphate tissue concentration. The results from this study thus suggest that for trained rats diets containing complex CH (compared with diets containing simple CH) improve the glycogenic capacity of liver and skeletal muscle, thus enabling the adequate regeneration of glycogen stores in these two tissues. 相似文献
4.
Role of the htrA gene in Klebsiella pneumoniae virulence 总被引:3,自引:0,他引:3
We recently described the use of mini-Tn5 to generate complement-sensitive mutants derived from a complement-resistant Klebsiella pneumoniae clinical isolate deficient in the lipopolysaccharide O side chain. One mutant with a reduced capacity to survive in nonimmune human sera carried the transposon inserted in the htrA gene. We cloned and sequenced the gene and predicted from the deduced amino acid sequence that the putative HtrA homolog contains structural features similar to those of previously described HtrA proteins. To investigate the biological functions and the role of the htrA gene in the virulence of K. pneumoniae, we constructed an isogenic mutant by insertion-duplication mutagenesis. Characterization of the mutant showed that it had greater sensitivity to temperature (50 degrees C) and oxidative stress (H(2)O(2)) than the parent strain. Furthermore, the htrA mutant produced less capsule, bound more molecules of complement component C3, and was more sensitive to complement and whole-blood killing than was the parent strain. Finally, disruption of the htrA gene in a virulent K. pneumoniae strain caused a reduction of its virulence in a mice model. Our results indicate that the htrA gene plays an important role in the virulence of K. pneumoniae. 相似文献
5.
de Astorza B Cortés G Crespí C Saus C Rojo JM Albertí S 《Infection and immunity》2004,72(3):1767-1774
The airway epithelium represents a primary site for contact between microbes and their hosts. To assess the role of complement in this event, we studied the interaction between the A549 cell line derived from human alveolar epithelial cells and a major nosocomial pathogen, Klebsiella pneumoniae, in the presence of serum. In vitro, we found that C3 opsonization of poorly encapsulated K. pneumoniae clinical isolates and an unencapsulated mutant enhanced dramatically bacterial internalization by A549 epithelial cells compared to highly encapsulated clinical isolates. Local complement components (either present in the human bronchoalveolar lavage or produced by A549 epithelial cells) were sufficient to opsonize K. pneumoniae. CD46 could competitively inhibit the internalization of K. pneumoniae by the epithelial cells, suggesting that CD46 is a receptor for the binding of complement-opsonized K. pneumoniae to these cells. We observed that poorly encapsulated strains appeared into the alveolar epithelial cells in vivo but that (by contrast) they were completely avirulent in a mouse model of pneumonia compared to the highly encapsulated strains. Our results show that bacterial opsonization by complement enhances the internalization of the avirulent microorganisms by nonphagocytic cells such as A549 epithelial cells and allows an efficient innate defense. 相似文献
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8.
Riera-Espinoza G Ramos J Carvajal R Belzares E Stanbury G Farías R Valderrama I Alvarez K Riera-González G 《Maturitas》2004,47(2):83-90
OBJECTIVES: An open study was carried out to evaluate changes in bone remodeling markers such as N-telopeptide (NTx), tartrate-resistant acid phosphatase (TRAP), total alkaline phosphatase (TAP), and bone alkaline phosphatase (BAP) during a 1-year continuous tibolone treatment in postmenopausal women. MATERIAL AND METHODS: Thirty-six postmenopausal women were recruited for receiving tibolone 2.5 mg per day for 1 year. Densitometry and determination of biochemical markers of bone metabolism in serum and urine were performed at 1, 3, 6, and 12 months. RESULTS: Comparing baseline with 12 month's values, BAP and all resorption markers decreased significantly. NTx began to decrease since the initiation of the treatment (baseline: 74.4 +/- 5.3; 1 month: 57.5 +/- 4.2; 12 months: 36.6 +/- 2.8). BAP increased at the first month (baseline: 37.3 +/- 2.1; 1 month: 42.6 +/- 3.0) but diminished in the following months (12 months: 23.1 +/- 1.5). TAP started to decrease significantly only after 6 months of treatment (baseline: 37.3 +/- 2.1; 12 months: 31.4 +/- 2.3) and TRAP after 3 months (baseline: 9.8 +/- 0.4; 6 months: 9.1 +/- 0.5; 12 months: 8.2 +/- 0.4). Normal bone mineral density at distal and ultradistal forearm was maintained during the 1-year treatment (baseline: 0.42 +/- 0.01; 12 months: 0.42 +/- 0.01 and baseline: 0.33 +/- 0.01; 12 months: 0.33 +/- 0.01, respectively). CONCLUSION: The use of tibolone 2.5 mg per day diminished progressively and significantly bone resorption and formation markers during 1-year treatment period. 相似文献
9.
Carlos M. Villaln Eduardo Ramírez‐San Juan Araceli Snchez‐Lpez Guadalupe Bravo Edwin W. Willems Pramod R. Saxena David Centurin 《Basic & clinical pharmacology & toxicology》2003,92(4):165-172
Abstract: The present study investigated the effects of dopamine on the canine external carotid circulation. One min. intracarotid artery (i.c.) infusions of dopamine (10–310 μg min.?1) produced dose‐dependent decreases in the canine external carotid conductance without affecting blood pressure or heart rate. This effect was mimicked by the D1/2‐like receptor agonist apomorphine (1–310 μg min?1), but not by the D2‐like receptor agonist, bromocriptine (31–310 μg min.?1). In contrast, fenoldopam (1–310 μg min.?1, intracarotid), a D1‐like receptor agonist, produced dose‐dependent increases in external carotid conductance. The vasoconstrictor response to dopamine was abolished after intravenous administration of the antagonists, phentolamine (α1/2; 2000 μg kg?1) or rauwolscine (α2; 100 μg kg?1), but remained unaffected after prazosin (α1; 100 μg kg?1) or haloperidol (D2‐like; 1000 μg kg?1). Interestingly, after phentolamine not only were the vasoconstrictor responses to dopamine abolished, but even a dose‐dependent vasodilator component was unmasked. These vasodilator responses to dopamine remained unchanged after intravenous haloperidol or propranolol (1000 μg kg?1 each). On the other hand, the vasodilator responses to fenoldopam, which remained unchanged after intravenous saline (0.1 ml kg?1), propranolol (1000 μg kg?1) or vagosympathectomy, were abolished by the D1‐like receptor antagonist, SCH‐23390 (10 μg kg?1). Lastly, the responses to dopamine and fenoldopam were not significantly altered after intraperitoneal pretreatment with reserpine (5 mg kg?1; ?24 hr). The above results suggest that the canine external carotid vasoconstrictor responses to dopamine: (i) are mainly mediated by α2‐adrenoceptors; and (ii) overshadow a vasodilator component, which involves vascular D1‐like receptors. 相似文献
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