Abstract:
:1. When injected intraperitoneally into mice in doses larger than those used clinically, all the amino derivatives of bisphosphonates (aminoBPs) tested induce a variety of inflammatory reactions such as induction of histidine decarboxylase (HDC, the histamine-forming enzyme), hypertrophy of the spleen, atrophy of the thymus, hypoglycaemia, ascites and accumulation of exudate in the thorax, and an increase in the number of macrophages and/or granulocytes in the peritoneal cavity of blood. On the other hand, dichloromethylene bisphosphonate (Cl2MBP) a typical non-aminoBP, has no such inflammatory actions. In the present study, we found that this agent can suppress the inflammatory actions of aminoBPs. 2. Cl2MBP, when injected into mice before or after injection of 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (AHBuBP; a typical aminoBP), inhibited the induction of HDC activity by AHBuBP in a dose- and time-dependent manner. The increase in HDC activity induced by AHBuBP was largely suppressed by the injection of an equimolar dose of Cl2MBP. Cl2MBP also inhibited other AHBuBP-induced inflammatory reactions, as well as the inflammatory actions of two other aminoBPs. However, Cl2MBP did not inhibit the increase in HDC activity induced by lipopolysaccharide (LPS). 3. We have previously reported that AHBuBP augments the elevation of HDC activity and the production of interleukin-1beta (IL-1beta) that are induced by LPS. These actions of AHBuBP were also inhibited by Cl2MBP. 4. Based on these results and reported actions of bisphosphonates, the mechanisms underlying the contrasting effects of aminoBPs and Cl2MBP, a non-aminoBP are discussed. The results suggest that combined administration of Cl2MBP and an aminoBP in patients might be a useful way of suppressing the inflammatory side effects of aminoBPs.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Endo Y,Shibazaki M,Yamaguchi K,Nakamura M,Kosugi Hdoi
10.1038/sj.bjp.0702367subject
Has Abstractpub_date
1999-02-01 00:00:00pages
903-10issue
4eissn
0007-1188issn
1476-5381journal_volume
126pub_type
杂志文章abstract::1. Cold storage (2 degrees C) treatment progressively reduced noradrenaline uptake by the taenia caecum of the guinea-pig. After 15 days of cold treatment, [(3)H]-noradrenaline uptake by tissue was reduced to about 10% of control. On the other hand, prolonged cold storage failed to decrease [(3)H]-adenosine uptake by ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08539.x
更新日期:1973-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Recently, we demonstrated that the nucleus accumbens (NAC) is required for the acquisition and expression of relief memory. The purpose of this study was to investigate the role of NMDA receptors within the NAC in relief learning. EXPERIMENTAL APPROACH:The NMDA receptor antagonist 2-amino-5-phos...
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1986.tb10176.x
更新日期:1986-01-01 00:00:00
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journal_title:British journal of pharmacology
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更新日期:1981-11-01 00:00:00
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abstract::The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand propert...
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journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
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更新日期:1994-09-01 00:00:00
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journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1973-02-01 00:00:00
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journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0701482
更新日期:1997-11-01 00:00:00
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更新日期:2001-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:1999-06-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1969-07-01 00:00:00
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journal_title:British journal of pharmacology
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abstract::GR231118 (also known as 1229U91 and GW1229), a purported Y(1) antagonist and Y(4) agonist was radiolabelled using the chloramine T method. [(125)I]-GR231118 binding reached equilibrium within 10 min at room temperature and remained stable for at least 4 h. Saturation binding experiments showed that [(125)I]-GR231118 b...
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更新日期:2000-01-01 00:00:00