Abstract：
BACKGROUND AND PURPOSE:Orally administered withanoside IV (a compound isolated from the roots of Withania somnifera) improved memory deficits in mice with a model of Alzheimer's disease induced by the amyloid peptide Abeta(25-35). Sominone, an aglycone of withanoside IV, was identified as an active metabolite after oral administration of withanoside IV. We aimed to identify receptors or associated molecules of sominone, and to investigate the effects of sominone on memory in normal mice. EXPERIMENTAL APPROACH:Phosphorylation levels of 71 molecules were compared between control and sominone-stimulated cortical cultured cells to search for target molecules of sominone. Object location memory and neurite density in the brain were evaluated in sominone-injected mice. KEY RESULTS:Phosphorylation of RET (a receptor for the glial cell line-derived neurotrophic factor, GDNF) was increased in neurons by sominone, without affecting the synthesis and secretion of GDNF. Knockdown of RET prevented sominone-induced outgrowths of axons and dendrites. After a single i.p. injection of sominone into normal mice, they could better memorize scenery information than control mice. Sixty minutes after sominone injection, RET phosphorylation was increased, particularly in the hippocampus of mice. After the memory tests, the densities of axons and dendrites were increased in the hippocampus by sominone administration. CONCLUSIONS AND IMPLICATIONS:Sominone could reinforce the morphological plasticity of neurons by activation of the RET pathway and thus enhance memory. Sominone, a compound with low molecular weight, may be a GDNF-independent stimulator of the RET pathway and/or a novel modulator of RET signalling.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Tohda C,Joyashiki Edoi
10.1111/j.1476-5381.2009.00313.xsubject
Has Abstractpub_date
2009-08-01 00:00:00pages
1427-40issue
8eissn
0007-1188issn
1476-5381pii
BPH313journal_volume
157pub_type
杂志文章abstract：:1. The effects of lifarizine (RS-87476) on intracellular Ca2+ rises and the release of glutamate from rat cerebrocortical synaptosomes depolarized with 30 mM KCl were investigated by use of entrapped fura 2 and exogenous glutamate dehydrogenase. 2. Prior (1 min) addition of lifarizine decreased 30 mM KCl-induced total...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15380.x
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abstract：:The arterial endothelium critically contributes to blood pressure control by releasing vasodilating autacoids such as nitric oxide, prostacyclin and a third factor or pathway termed 'endothelium-derived hyperpolarizing factor' (EDHF). The nature of EDHF and EDHF-signalling pathways is not fully understood yet. However...
journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1971.tb09934.x
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abstract：:1. In this study 3 protocols were utilized to determine the role of endogenous kinins in the resistance of the inbred Dahl (Rapp) salt-resistant (SR/Jr) rats to high salt diet-induced blood pressure elevation. 2. The bradykinin B2 receptor antagonist, Hoe 140 (D-Arg[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin) at doses of ei...
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pub_type： 杂志文章
doi：10.1038/sj.bjp.0701797
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abstract：:Antibiotics are an essential part of modern medicine. The emergence of antibiotic-resistant mutants among bacteria is seemingly inevitable, and results, within a few decades, in decreased efficacy and withdrawal of the antibiotic from widespread usage. The traditional answer to this problem has been to introduce new a...
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journal_title：British journal of pharmacology
pub_type： 杂志文章
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abstract：:1. [3H]-ouabain uptake in resting guinea-pig papillary muscles depended directly on incubation time and inversely with muscle radius. The equivalence of both parameters support the relevance of diffusion. A particular mechanism of receptor-controlled diffusion was implicated by the saturation of initial rates of uptak...
journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1992.tb13428.x
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abstract：:(1) Here, we introduce a beta-casomorphin-5-derived cyclic pentapeptide, cCD-2 (Tyr-cyclo[d-Orn-Tyr(Bzl)-Pro-Gly]), which inhibits the cell growth of a variety of human cancer cell lines. (2) This opioid-derived peptide possesses only low affinity for mu-receptors, but enhances the agonist binding to mu-receptors in v...
journal_title：British journal of pharmacology
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doi：10.1038/sj.bjp.0705416
更新日期：2003-09-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14128.x
更新日期：1990-11-01 00:00:00
abstract：:1. The mechanism of stimulation of cyclic adenosine 3',5'-monophosphate (cyclic AMP) accumulation by adrenaline and ouabain and the effect of Mn(++) substitution for Mg(++) as the metal ion requirement of this system was studied in cell-free preparations of adenyl cyclase from rat brain.2. In the rat cerebral cortex p...
journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1973.tb08358.x
更新日期：1973-07-01 00:00:00
abstract：:1. Microvascular permeability in the mesentery and consequent leakage of protein into the peritoneum of spontaneously hypertensive rats (SHR) and normotensive rats (NTR) was measured in vivo by the extravasation of Evans blue dye. 2. In sensitized NTR, challenge with antigen produced extensive increases in dye extrava...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701875
更新日期：1998-06-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705940
更新日期：2004-12-01 00:00:00
abstract：:Although previous reports have suggested that the sigma 1 (sigma(1)) receptor may be involved in pain sensation, its specific site of action has not been elucidated. The aim of present study was to determine the role of the spinal sigma(1) receptor in formalin-induced pain behavior, spinal cord Fos expression and phos...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706764
更新日期：2006-06-01 00:00:00
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1993.tb13447.x
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journal_title：British journal of pharmacology
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更新日期：2006-01-01 00:00:00
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更新日期：2008-07-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.13651
更新日期：2016-12-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0700931
更新日期：1997-02-01 00:00:00
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1990.tb12103.x
更新日期：1990-09-01 00:00:00
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journal_title：British journal of pharmacology
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doi：10.1038/bjp.2008.227
更新日期：2008-09-01 00:00:00
abstract：:A new C5a receptor antagonist, the cyclic peptide Phe-[Orn-Pro-D-cyclohexylalanine-Trp-Arg], (F-[OPdChaWR]), was tested for its ability to antagonize the neutropenic effects of both C5a and endotoxin in rats. Human recombinant C5a (2 microg kg(-1) i.v.) caused rapid neutropenia, characterized by an 83% decrease in cir...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702338
更新日期：1999-02-01 00:00:00
abstract：:1. The NK1 tachykinin receptor agonists, septide, [Sar9,Met(O2)11]SP and [Pro9]SP produced locomotor hyperactivity (10-20 min) when injected intracerebroventricularly (i.c.v.) in the guinea-pig. The most potent in eliciting this hyperactivity was septide (from 0.63 to 5 micrograms), compared to [Sar9,Met(O2)11]SP, whi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15101.x
更新日期：1995-11-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1984.tb10766.x
更新日期：1984-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Picomolar concentrations of the beta3-adrenoceptor agonist BRL37344 stimulate 2-deoxyglucose uptake in soleus muscle via undefined receptors. Higher concentrations alter uptake, apparently via beta2-adrenoceptors. Effects of BRL37344 and beta2-adrenoceptor agonists are compared. EXPERIMENTAL APP...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.244
更新日期：2008-10-01 00:00:00
