Anorexic response to rapamycin does not appear to involve a central mechanism.

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.

authors

Toklu HZ,Bruce EB,Sakarya Y,Carter CS,Morgan D,Matheny MK,Kirichenko N,Scarpace PJ,Tümer N

doi

10.1111/1440-1681.12601

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

802-7

issue

9

eissn

0305-1870

issn

1440-1681

journal_volume

43

pub_type

杂志文章
  • Salt and water intake and sodium and potassium excretion in spontaneously hypertensive rats.

    abstract::1. Total fluid and saline intakes were greater in spontaneously hypertensive rats (SHR) than in normotensive rats (NTR). 2. Total fluid and saline intake were significantly elevated in prehypertensive SHR, 5 weeks old, compared with age-matched NTR, and the intakes fell with age in both strains but remained considerab...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1681.1983.tb00172.x

    authors: May CN,Parsons BJ

    更新日期:1983-01-01 00:00:00

  • Noradrenergic reinnervation of the rat vas deferens after vasovasostomy following vasectomy.

    abstract::1. Anastomosis (vasovasostomy) of epididymal and prostatic halves of vasa deferentia was carried out in rats in which unilateral or bilateral medial transection (vasectomy) had been performed 4 weeks previously. 2. Noradrenaline levels in epididymal halves of vasa deferentia, 8 weeks after anastomosis with prostatic h...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1681.1987.tb00984.x

    authors: DeGaris RM,Pennefather JN

    更新日期:1987-05-01 00:00:00

  • Effects of econazole on Ca2+ levels in and the growth of human prostate cancer PC3 cells.

    abstract::1. Econazole is used clinically as an antifungal drug with many different in vitro effects. However, the effects of econazole on prostate cancer cells are unknown. The effects of econazole on intracellular Ca2+ concentrations ([Ca2+]i) in and the proliferation of human PC3 prostate cancer cells was explored in the pre...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1681.2005.04254.x

    authors: Huang JK,Liu CS,Chou CT,Liu SI,Hsu SS,Chang HT,Hsieh CH,Chang CH,Chen WC,Jan CR

    更新日期:2005-09-01 00:00:00

  • Effect of acute administration of prazosin on blood pressure, heart rate and plasma renin level in the conscious normotensive rat.

    abstract::This study investigated whether the specific alpha-antagonist, prazosin, stimulated basal plasma renin levels and heart rate. Furthermore the beta-adrenergic nervous system was also investigated to ascertain whether it was involved in this effect. Prazosin (0.1 or 1 mg/kg) was injected subcutaneously (s.c.) to conscio...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1681.1986.tb00936.x

    authors: Atkinson J,Luthi P,Sonnay M,Boillat N

    更新日期:1986-07-01 00:00:00

  • Unexpected incidence of low blood pressure 2 years after unilateral adrenalectomy for primary aldosteronism.

    abstract::1. Serial observations of blood pressure after unilateral adrenalectomy for aldosterone-producing adenoma revealed an incidence of hypotension (systolic BP less than fifth percentile for age- and sex-matched normal population) of 27% at 2 years, more than 5 times that predicted. 2. Serial observations of volume regula...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1681.1989.tb01558.x

    authors: Gordon RD,Hawkins PG,Hamlet SM,Tunny TJ,Klemm SA,Backmann AW,Finn WL

    更新日期:1989-04-01 00:00:00

  • Implications of cross-talk between tumour necrosis factor and insulin-like growth factor-1 signalling in skeletal muscle.

    abstract::1. Inflammation, particularly the pro-inflammatory cytokine tumour necrosis factor (TNF), increases necrosis of skeletal muscle. Depletion of inflammatory cells, such as neutrophils, cromolyn blockade of mast cell degranulation or pharmacological blockade of TNF reduces necrosis of dystrophic myofibres in the mdx mous...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1440-1681.2007.04868.x

    authors: Grounds MD,Radley HG,Gebski BL,Bogoyevitch MA,Shavlakadze T

    更新日期:2008-07-01 00:00:00

  • Studies of evolutionary temperature adaptation: muscle function and locomotor performance in Antarctic fish.

    abstract::1. Studies of evolutionary temperature adaptation of muscle and locomotor performance in fish are reviewed with a focus on the Antarctic fauna living at subzero temperatures. 2. Only limited data are available to compare the sustained and burst swimming kinematics and performance of Antarctic, temperate and tropical s...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1440-1681.1998.tb02291.x

    authors: Franklin CE

    更新日期:1998-09-01 00:00:00

  • β-lactam pharmacokinetics and pharmacodynamics in critically ill patients and strategies for dose optimization: a structured review.

    abstract::1. Infections and related sepsis are two of the most prevalent issues in the care of critically ill patients, with mortality as high as 70%. Appropriate antibiotic selection, as well as adequate dosing, is important to improve the clinical outcome for these patients. 2. β-Lactams are the most common antibiotic class u...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1440-1681.2012.05715.x

    authors: Sinnollareddy MG,Roberts MS,Lipman J,Roberts JA

    更新日期:2012-06-01 00:00:00

  • Inhibition of nuclear translocation of transcription factor nuclear factor-kappa B induces FAS- as well as tumour necrosis factor-alpha-mediated apoptosis through downregulation of a conserved family of inhibitor of apoptosis 1.

    abstract::1. In the present study, we examined whether the nuclear transcription factor (NF)-kappaB activity plays a role in the determination of sensitivity to tumour necrosis factor (TNF)-alpha or agonistic Fas antibody (Ab) in human vascular smooth muscle cells (hVSMC). 2. To inhibit agonist-induced NF-kappaB activation in h...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1046/j.1440-1681.2003.03817.x

    authors: Imanishi T,Hano T,Takarada S,Nishio I

    更新日期:2003-03-01 00:00:00

  • Ionic mechanisms regulating sodium entry into vascular smooth muscle.

    abstract::1. Na+/H+ exchange, an ethylisopropylamiloride (EIPA)-sensitive Na+ and HCO3- dependent system and a diisothio-cyanatostilbenedisulphonic acid (DIDS)-sensitive Na+ and HCO3- transporter, contribute to sodium influx and intracellular pH (pHi) regulation in vascular smooth muscle. 2. In cultured cells from the human int...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1440-1681.1991.tb01419.x

    authors: Bobik A,Little PJ,Neylon CB

    更新日期:1991-02-01 00:00:00

  • Dual nitric oxide mechanisms of cholestasis-induced bradycardia in the rat.

    abstract::1. Cholestatic liver disease is associated with nitric oxide (NO) overproduction and bradycardia. Nitric oxide has a dual effect on sinoatrial node and its effects depend on its concentration. Nitric oxide can increase heart rate by activating hyperpolarization-activated pacemaker current (If) but, at high concentrati...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1046/j.1440-1681.2002.03748.x

    authors: Mani AR,Nahavandi A,Moosavi M,Safarinejad R,Dehpour AR

    更新日期:2002-10-01 00:00:00

  • The CGP7930 analogue 2,6-di-tert-butyl-4-(3-hydroxy-2-spiropentylpropyl)-phenol (BSPP) potentiates baclofen action at GABA(B) autoreceptors.

    abstract::The pharmacological actions of 2,6-di-tert-butyl-4-(3-hydroxy-2-spiropentylpropyl)-phenol (BSPP), a putative presynaptic GABA(B) receptor modulator, were examined in electrically stimulated rat neocortical brain slices preloaded with [3H]-GABA or [3H]-glutamic acid. At 10 mmol/L, BSPP inhibited the release of [3H]-GAB...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1681.2008.04948.x

    authors: Parker DA,Marino V,Ong J,Puspawati NM,Prager RH

    更新日期:2008-09-01 00:00:00

  • Plasma and tissue iron changes in the rat after acute administration of ethionine.

    abstract::1. Ethionine administered acutely to the adult female rat markedly elevates and then lowers plasma iron concentration over several days. Liver iron undergoes a reverse cycle. 2. Ethionine does not cause changes in the blood parameters, including total plasma iron-binding capacity and plasma iron clearance. Erythrocyte...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1681.1975.tb01851.x

    authors: Loh TT,Archdeacon JW

    更新日期:1975-11-01 00:00:00

  • Toxic marine dinoflagellates in Singapore waters that cause seafood poisonings.

    abstract::1. The present paper reviews the toxic dinoflagellates found in Singapore waters that produce toxins that can accumulate through marine food chains to cause seafood poisonings. 2. Singapore waters contain dinoflagellate species linked to three types of seafood poisoning: paralytic shellfish poisoning, diarrhetic shell...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审

    doi:10.1046/j.1440-1681.2002.03724.x

    authors: Holmes MJ,Teo SL

    更新日期:2002-09-01 00:00:00

  • Brain and retinal microglia in health and disease: an unrecognized target of the renin-angiotensin system.

    abstract::Microglia are the resident immune cells within the brain and retina, commonly known as the macrophages of the central nervous system (CNS). Microglia survey the surrounding milieu to eliminate invading microbes, clear cellular debris and enforce programmed cell death by removing apoptotic cells. Complementary to their...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审

    doi:10.1111/1440-1681.12099

    authors: McCarthy CA,Widdop RE,Deliyanti D,Wilkinson-Berka JL

    更新日期:2013-08-01 00:00:00

  • Role of calcium-activated potassium channels in the relaxation of tracheal smooth muscles by forskolin.

    abstract::1. The role of calcium-activated potassium (KCa) channels in bronchodilation produced by a direct adenylyl cyclase activator, forskolin, was investigated. The involvement of intracellular cyclic AMP (cAMP) in the process was also examined. 2. The isometric tension records from guinea-pig tracheal smooth muscles indica...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1681.1994.tb02529.x

    authors: Hiramatsu T,Kume H,Kotlikoff MI,Takagi K

    更新日期:1994-05-01 00:00:00

  • Renal function in adult rats subjected to prenatal dexamethasone.

    abstract::1. Prenatal dexamethasone leads to low birth weight and compromises organogenesis, but its effects on nephrogenesis in male and female rats have not yet been investigated extensively. Reduced renal mass may be responsible for hypertension and renal haemodynamic and morphological adjustments to maintain the glomerular ...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1046/j.1440-1681.2003.03787.x

    authors: Martins JP,Monteiro JC,Paixão AD

    更新日期:2003-01-01 00:00:00

  • Enhancement by endothelin-1 of the release of catecholamines from the canine adrenal gland in response to splanchnic nerve stimulation.

    abstract::1. The effect of endothelin-1 on the release of adrenal catecholamines was examined in anaesthetized dogs. 2. Splanchnic nerve stimulation (SNS) at 1 and 3 Hz was applied before and after the intravenous injection of endothelin-1. 3. Endothelin-1 (0.1 and 0.3 micrograms/kg) significantly enhanced the release of adrena...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1681.1992.tb00519.x

    authors: Takeuchi A,Kimura T,Satoh S

    更新日期:1992-09-01 00:00:00

  • New diagnostic tests for Cushing's syndrome: uses of naloxone, vasopressin and alprazolam.

    abstract::1. We set out to investigate whether the administration of naloxone alone, naloxone plus vasopressin (AVP) or naloxone plus alprazolam to patients with Cushing's syndrome would result in a blunted dynamic response of the pituitary-adrenal axis compared with normal volunteers. Cushing's syndrome is often difficult to d...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 临床试验,杂志文章

    doi:10.1111/j.1440-1681.1996.tb02785.x

    authors: Jackson RV,Hockings GI,Torpy DJ,Grice JE,Crosbie GV,Walters MM,Strakosch CR

    更新日期:1996-06-01 00:00:00

  • Hypertonicity increases rabbit atrium and pulmonary vein arrhythmogenesis: a potential contributor to the genesis of atrial fibrillation.

    abstract::1. Pulmonary veins are the most important focus for the initiation of atrial fibrillation. Diabetes mellitus may be associated with hypertonicity and increased occurrence of atrial fibrillation. 2. The purpose of the present study was to investigate whether hypertonicity alters the electrophysiological characteristics...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1681.2008.05085.x

    authors: Lee SH,Chen YC,Cheng CC,Higa S,Chen YJ,Chen SA

    更新日期:2009-04-01 00:00:00

  • Cardiovascular status following combined angiotensin-converting enzyme and AT1 receptor inhibition in conscious spontaneously hypertensive rats.

    abstract::1. Combined treatment of spontaneously hypertensive rats (SHR) with AT1 receptor antagonists and angiotensin-converting enzyme (ACE) inhibitors has been shown to reduce mean arterial pressure (MAP) more than monotherapy with either agent. The aims of the present study were to investigate the effects of chronic dual re...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1046/j.1440-1681.2003.03837.x

    authors: Duke LM,Paull JR,Widdop RE

    更新日期:2003-05-01 00:00:00

  • Taurine inhibits development of atherosclerotic lesions in apolipoprotein E-deficient mice.

    abstract::1. The effects of taurine on the development of atherosclerotic lesions were investigated in apolipoprotein (apo) E-deficient mice, an animal model with severe hypercholesterolaemia and extensive atherosclerosis. These mice were fed a normal laboratory chow containing 2% taurine for 12 weeks. 2. Serum total cholestero...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1046/j.1440-1681.2001.03527.x

    authors: Kondo Y,Toda Y,Kitajima H,Oda H,Nagate T,Kameo K,Murakami S

    更新日期:2001-10-01 00:00:00

  • Rilmenidine acts as a partial agonist at prejunctional alpha 2-adrenoceptors in guinea-pig atria.

    abstract::1. The present study was carried out to determine whether rilmenidine, a recently introduced antihypertensive agent which acts on alpha 2-adrenoceptors, has partial agonist activity on prejunctional alpha 2-adrenoceptors in guinea-pig atria. 2. Isolated preparations of guinea-pig atria were incubated with [3H]-noradre...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1681.1988.tb01016.x

    authors: Li CG,Rand MJ

    更新日期:1988-10-01 00:00:00

  • Quercetin activates human Kv1.5 channels by a residue I502 in the S6 segment.

    abstract::1. The aims of the present study were to investigate the pharmacological effects of quercetin on wild-type (WT) and mutant (I502A) human (h) Kv1.5 channel currents (I(kur)) and to identify whether mutation in the S6 segment is critical to activation of I(kur) by quercetin. 2. Experiments were performed on WT and site-...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1681.2008.05061.x

    authors: Yang L,Ma JH,Zhang PH,Zou AR,Tu DN

    更新日期:2009-02-01 00:00:00

  • Investigation of class I anti-arrhythmic drug actions on guinea-pig cardiac mitochondrial lactate dehydrogenase activity.

    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 ...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1681.1993.tb01671.x

    authors: Dzimiri N,Almotrefi AA

    更新日期:1993-04-01 00:00:00

  • Effects of dopamine and nitric oxide on arterial pressure and renal function in volume expansion.

    abstract::1. The aim of the present study was to investigate the role of dopamine (DA) in the hypotensive and renal effects of L-arginine during extracellular fluid volume expansion (10% bodyweight). 2. Animals were randomized to non-expanded and expanded groups. Both groups received different treatments: L-arginine (250 mg/kg,...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1046/j.1440-1681.2002.03729.x

    authors: Costa Mde L,Loria A,Marchetti M,Balaszczuk AM,Arranz CT

    更新日期:2002-09-01 00:00:00

  • The inhibitory response of the rabbit anococcygeus muscle.

    abstract::1. Strips of rabbit anococcygeus muscle were submaximally contracted by the addition of phenylephrine to the bath fluid. 2. Acetylcholine, dimethylphenylpiperazinium and electrical field stimulation caused relaxation. Relaxation induced by acetylcholine and field stimulation was blocked by tetrodotoxin but only the ac...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1681.1976.tb00598.x

    authors: Wai SS,Coupar IM

    更新日期:1976-03-01 00:00:00

  • Influence of low and normal appendicular lean mass on central blood pressure and wave reflection responses to muscle metaboreflex activation in postmenopausal women.

    abstract::Sarcopenia, defined by reduced appendicular skeletal muscle mass (ASM)/height2 (ASMI), is associated with increased arterial stiffness (brachial-ankle pulse wave velocity, baPWV) and wave reflection (augmentation index, AIx). Blood pressure (BP) responses to metaboreflex activation (post-exercise muscle ischemia, PEMI...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 信件

    doi:10.1111/1440-1681.12655

    authors: Figueroa A,Alvarez-Alvarado S,Jaime SJ,Johnson SA,Campbell JC,Feresin RG,Elam ML,Navaei N,Pourafshar S,Arjmandi BH

    更新日期:2016-12-01 00:00:00

  • The association between serum albumin/prealbumin level and disease severity in non-CF bronchiectasis.

    abstract::Non-cystic fibrosis (non-CF) bronchiectasis is a chronic pulmonary disease that can lead to malnutrition. Serum prealbumin and albumin level are related to inflammatory and nutritional status. Thus, we aimed to confirm our hypothesis that low serum albumin and prealbumin level, as well as body mass index (BMI), is cor...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/1440-1681.13331

    authors: Li L,Li Z,Bi J,Li H,Wang S,Shao C,Song Y

    更新日期:2020-09-01 00:00:00

  • Effects of thyroid hormones, antithyroid drugs and iodide on in vitro conversion of thyroxine to triiodothyronine.

    abstract::In an attempt to study the effects of thyroid hormones, antithyroid drugs and iodide on the conversion of thyroxine (T4) to triiodothyronine (T3), the liver was obtained from normal, hypothyroid and hyperthyroid rats treated with T4 or T3 . T4 was incubated with liver homogenates and generated T3 was measured. 1. The ...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1681.1981.tb00154.x

    authors: Aizawa T,Yamada T

    更新日期:1981-05-01 00:00:00