Abstract:
AIM:To investigate modulation of antagonist and agonist binding to adenosine A1 receptors by MgCl2 and 5 -guanylimidodiphosphate (Gpp(NH)p) using rat brain membranes and the A1 antagonist [3H]-8-cyclopentyl-1,3-dipropylxanthine ([3H]DPCPX) and the A1 agonist [3H]-2-chloro-N6-cyclopentyladenosine ([3H]CCPA). METHODS:Parallel saturation and inhibition studies were performed using well-characterised radioligand binding assays and a Brandel Cell Harvester. RESULTS:MgCl2 produced a concentration-dependent decrease (44%), whereas Gpp(NH)p increased [3H]DPCPX binding (19%). In [3H]DPCPX competition studies, agonist affinity was 1.5-14.6-fold higher and 4.6-10-fold lower in the presence of 10 mmol/L MgCl2 and 10 micromol/L Gpp(NH)p respectively; antagonist affinity was unaffected. The decrease in agonist affinity with increasing Gpp(NH)p concentrations was due to a reduction in the proportion of binding to the high affinity receptor state. In contrast to [3H]DPCPX, MgCl2 produced a concentration-dependent increase (72%) and Gpp(NH)p a decrease (85%) in [3H]CCPA binding. Using [3H]CCPA, agonist affinities were 5-17-fold higher than those for [3H]DPCPX, consistent with binding only to the high affinity receptor state. Agonist affinity was 1.3-10.5-fold higher and 2.4-4.7-fold lower on adding MgCl2 or Gpp(NH)p respectively; antagonist affinities were as for [3H]DPCPX. CONCLUSION:The inconsistencies surrounding the effects of MgCl2 and guanine nucleotides on radioligand binding to adenosine A1 receptors were systematically examined. The effects of MgCl2 and Gpp(NH)p on agonist binding to A1 receptors are consistent with their roles in stimulating GTP-hydrolysis at the G-protein alpha-subunit and in blocking formation of the high affinity agonist-receptor-G protein complex.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Finlayson K,Maemoto T,Butcher SP,Sharkey J,Olverman HJsubject
Has Abstractpub_date
2003-08-01 00:00:00pages
729-40issue
8eissn
1671-4083issn
1745-7254journal_volume
24pub_type
杂志文章abstract:AIM:To examine the in vitro antitumor activity of resveratrol against multiple myeloma (MM) cell lines (RPMI 8226, U266, and KM3), and the mechanisms involved. METHODS:The growth inhibition of resveratrol was determined by 3-(4, 5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The effect of resve...
journal_title:Acta pharmacologica Sinica
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更新日期:2006-11-01 00:00:00
abstract::An early intervention using biomarkers to predict acute myocardial infarction (AMI) will effectively reduce global heart attack incidence, particularly among high-risk patients with type 2 diabetes mellitus (T2DM). This study attempted to identify potential biomarkers by detecting changes in the levels of plasma prote...
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journal_title:Acta pharmacologica Sinica
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更新日期:2017-07-01 00:00:00
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abstract:AIM:To Study the interaction of macrophage colony-stimulating factor (M-CSF) and interleukin-10 (IL-10) in productions of IL-12 and IL-18 and expressions of CD14, CD23, and CD64 by human monocytes. METHODS:Purified adherent human monocytes were cultured with M-CSF or IL-10 alone, or with M-CSF+IL-10 and 2-3d later, th...
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abstract:AIM:To investigate whether nimesulide could suppress tumor growth and induce apoptosis in implanted hepatoma mice and to explore the molecular mechanisms. METHODS:Male mice received nimesulide 10 mg/kg, 20 mg/kg, and 40 mg/kg ig daily for 21 d. Electron microscopy (EM), flow cytometry (FCM), DNA ladder, radioimmunoass...
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doi:
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pub_type: 杂志文章
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pub_type: 临床试验,杂志文章
doi:
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pub_type: 杂志文章,收录出版
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doi:
更新日期:2002-11-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2009.47
更新日期:2009-06-01 00:00:00
abstract::Pre-B-cell leukemia transcription factor 3 (PBX3) is a member of the PBX family and contains a highly conserved homologous domain. PBX3 is involved in the progression of gastric cancer, colorectal cancer, and prostate cancer; however, the detailed mechanism by which it promotes tumor growth remains to be elucidated. H...
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pub_type: 临床试验,杂志文章
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更新日期:2013-07-01 00:00:00
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更新日期:2014-02-01 00:00:00
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更新日期:2008-01-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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更新日期:2018-09-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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更新日期:2015-12-01 00:00:00
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更新日期:2015-03-01 00:00:00
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journal_title:Acta pharmacologica Sinica
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-09-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00