Abstract:
:The authors have previously demonstrated that a low and intermittent peripheral dose of rapamycin (1 mg/kg three times/week) to rats inhibited mTORC1 signalling, but avoided the hyperlipidemia and diabetes-like syndrome associated with higher doses of rapamycin. The dosing regimen reduced food intake, body weight, adiposity, serum leptin and triglycerides. mTORC1 signalling was inhibited in both liver and hypothalamus, suggesting some of the actions, in particular the decrease in food intake, may be the results of a central mechanism. To test this hypothesis, rapamycin (30 μg/day for 4 weeks) was infused into 23-25-month-old F344xBN rats by intracerebroventricular (icv) mini pumps. Our results demonstrated that central infusion did not alter food intake or body weight, although there was a tendency for a decrease in body weight towards the end of the study. mTORC1 signalling, evidenced by decreased phosphorylation of S6 protein at end of 4 weeks, was not activated in liver, hypothalamus or hindbrain. Fat and lean mass, sum of white adipose tissues, brown adipose tissue, serum glucose, insulin and leptin levels remained unchanged. Thus, these data suggest that the anorexic and body weight responses evident with peripheral rapamycin are not the result of direct central action. The tendency for decreased body weight towards the end of study, suggests that there is either a slow transport of centrally administered rapamycin into the periphery, or that there is delayed action of rapamycin at sites in the brain.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Toklu HZ,Bruce EB,Sakarya Y,Carter CS,Morgan D,Matheny MK,Kirichenko N,Scarpace PJ,Tümer Ndoi
10.1111/1440-1681.12601subject
Has Abstractpub_date
2016-09-01 00:00:00pages
802-7issue
9eissn
0305-1870issn
1440-1681journal_volume
43pub_type
杂志文章abstract::Ventilation to one lobe of lung was reduced in anaesthetized open-chest cats and dogs to simulate the ventilation/perfusion (V/Q) mismatching of chronic lung disease. Blood flow to this lobe fell less than ventilation; thus lobar V/Q diminished. In seven cats almitrine (0.5 mg/kg + 10 micrograms/kg per min, i.v.) caus...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1986.tb00926.x
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abstract::1. During the destruction of articular cartilage, fibrinolytic enzymes and matrix metalloproteinases (MMP) may contribute to the related pathology. The activities, antigens and messenger RNA (mRNA) levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in articular cartilage...
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doi:10.1111/j.1440-1681.1996.tb01138.x
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doi:10.1111/j.1440-1681.2006.04510.x
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1981.tb00750.x
更新日期:1981-09-01 00:00:00
abstract::1. There is mounting evidence that a wide range of antidepressants share the common feature of increasing hippocampal neurogenesis. The specificity of this association has suggested that an ability to increase neurogenesis might be a useful paradigm to screen for compounds with antidepressant activity. 2. The hope of ...
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 更正并重新发布的文章,杂志文章
doi:
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1986.tb02392.x
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abstract::1. The functional innervation of autonomic target tissues occurs early during development, at a time when both the nerves and post-synaptic target tissues are still differentiating. 2. Physiological responses appear soon after the arrival of the first fibres when uptake and release mechanisms within the nerves are alr...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.1999.03092.x
更新日期:1999-08-01 00:00:00
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doi:10.1111/1440-1681.12582
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doi:10.1111/1440-1681.13449
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pub_type: 杂志文章,meta分析
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pub_type: 杂志文章
doi:10.1111/j.1440-1681.1995.tb01912.x
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1976.tb00624.x
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pub_type: 杂志文章
doi:10.1111/j.1440-1681.1998.tb02229.x
更新日期:1998-06-01 00:00:00
abstract::1. Angiotensin (Ang)II is involved in responses to hypovolaemia, such as sodium appetite and increase in blood pressure. Target areas subserving these responses for AngII include the cardiovascular system in the periphery and the circumventricular organs in the brain. 2. Conflicting data have been reported for the rol...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
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更新日期:2000-05-01 00:00:00
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doi:10.1111/1440-1681.13133
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pub_type: 杂志文章
doi:10.1111/j.1440-1681.1990.tb01325.x
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pub_type: 杂志文章
doi:10.1111/j.1440-1681.1993.tb01661.x
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journal_title:Clinical and experimental pharmacology & physiology
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pub_type: 杂志文章
doi:10.1111/j.1440-1681.2010.05443.x
更新日期:2010-12-01 00:00:00
abstract::1. The effects of the Class I anti-arrhythmic drugs quinidine, procainamide, lidocaine, phenytoin and tocainide on mitochondrial lactate dehydrogenase activity were compared in guinea-pig heart preparations. 2. All the tested drugs inhibited the enzyme activity in a concentration-dependent fashion, exhibiting varying ...
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pub_type: 杂志文章
doi:10.1111/j.1440-1681.1993.tb01671.x
更新日期:1993-04-01 00:00:00
abstract::1. In order to find an anaesthesia with minimum perturbation to the metabolism of chylomicrons, the effects of seven different anaesthetic agents on clearance from plasma of chylomicron-like emulsions were compared. 2. Avertin, urethane, fentanyl, and a ketamine/xylazine mixture all slowed the removal from plasma of e...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1993.tb01502.x
更新日期:1993-01-01 00:00:00
abstract::1. Taurine and homocysteine are metabolites of methionine. Hyperhomocysteinaemia is one of the risk factors for cardiovascular disease. Although taurine may be a cardiovascular cytoprotective substance, we hypothesized that it may antagonize the effects of homocysteine on myocardial mitochondrial function. 2. We studi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
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更新日期:2004-04-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1994.tb02515.x
更新日期:1994-04-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.04866.x
更新日期:2008-07-01 00:00:00
abstract::1. Phytoncides are volatile substances released mainly from trees. We studied whether phytoncides can reduce stress responses in stroke-prone spontaneously hypertensive rats (SHRSP). 2. Under the restraint stress, SHRSP exposed to phytoncides showed lower blood pressure than those without the exposure (186.8 +/- 3.9 v...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2004.04102.x
更新日期:2004-12-01 00:00:00
abstract::1. The study examines whether intracerebroventricular (ICV) infusion of atrial natriuretic peptide (human ANP,1-28) influences renal electrolyte and water excretion, vasopressin release, renal and femoral blood flows in conscious ewes. The blood flow was measured by chronically implanted ultrasonic flow probes. 2. ICV...
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pub_type: 杂志文章
doi:10.1111/j.1440-1681.1994.tb02494.x
更新日期:1994-03-01 00:00:00