The Histamine H_2-Receptor Antagonist, Cimetidine, Inhibits the Articular Osteopenia in Rats With Adjuvant-Induced Arthritis by Suppressing the Osteoclast Differentiation Induced by Histamine
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概要
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The effects of cimetidine on rat adjuvant arthritis (AA) and rat osteoclast differentiation were studied. For the in vivo experiments, AA was induced by injections of Mycobacterium tuberculosis H37RA either subcutaneously into the base of the tail or into the right hind paw. The osteoclast differentiation was assessed by estimating the number of tartrate-resistant acid phosphatase-positive multinuclear cells in the bone marrow culture. Cimetidine, at the dose of 25 mg/kg body weight, reduced the paw swelling by 70% (P<0.01). Cimetidine, at 10 μM concentration, inhibited 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) and histamine mediated osteoclast differentiations by 40% (P<0.01) and 60% (P<0.001), respectively. Dimaprit, at 0.3 μM, stimulated the cell differentiation by 100% (P<0.01). Mepyramine reduced osteoclast differentiation, but the reduction was not statistically significant. Measurements of bone mineral density of the femur indicated that 5 mg/kg of cimetidine treated animals had 30% (P<0.01) higher mineral density in comparison with that of the AA control group that received no cimetidine. These results suggest that histamine is a potent inducer of osteoclast differentiation, at least in part, through the histamine H2-receptor, and cimetidine has a preventive effect on articular destruction and accompanying inflammation in arthritic rats. These observations may provide critical insights into the pathogenesis of the bone pathology seen in patients with RA.
- 社団法人 日本薬理学会の論文
- 2003-05-01
著者
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Ueno K
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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YONEKAWA Taeko
Department of Geriatric Pharmacology & Therapeutics, Graduate School of Pharmaceutical Sciences, Chi
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Yonekawa Taeko
Geriatric Pharmacology & Therapeutics Graduate School Of Pharmaceutical Sciences Chiba Universit
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Ueno K
Laboratory Of Biochemical Pharmacology And Biotoxicology Faculty Of Pharmaceutical Sciences Chiba Un
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Ueno Koichi
Laboratory Of Biochemical Pharmacology And Biotoxicology Department Of Drug Evaluation And Toxicolog
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Ueno Koichi
Departments Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Ch
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Yano S
Laboratory Of Molecular Pharmacology And Pharmacotherapeutics Graduate School Of Pharmaceutical Scie
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Ueno Koichi
Department Of Drug Evaluation And Toxicological Sciences Faculty Of Pharmaceutical Sciences Chiba Un
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Nakamura Tomonori
千葉大学 薬学研究院高齢者薬物学
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Nakamura Tomonori
Department Of Molecular Pharmacology And Pharmacotherapeutics Graduate School Of Pharmaceutical Scie
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Yano Shingo
Laboratory Of Molecular Pharmacology And Pharmacotherapeutics Graduate School Of Pharmaceutical Scie
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Ueno K
Kinki Univ. Nara Jpn
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Ueno Koichi
Dep. Of Geriatric Pharmacology Graduate School Of Pharmaceutical Sciences Chiba Univ.
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Yamaura Katsunori
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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Yamaura Katsunori
Department Of Geriatric Pharmacology & Therapeutics Graduate School Of Pharmaceutical Sciences C
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Nakamura Tomonori
Dept Of Mol. Pharmacol. & Pharmacother Grad. Sch. Pharm. Sci. Chiba Univ.
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Yano Shingo
Department Of Molecular Pharmacology And Pharmacotherapeutics Graduate School Of Pharmaceutical Scie
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Yano Shingo
Department Of Drug Evaluation And Toxicological Sciences Faculty Of Pharmaceutical Sciences Chiba Un
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Ueno Koichi
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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Nakamura Tomonori
Department of Bioengineering and Robotics, Tohoku University, 01 Aza Aoba, Aramaki, Aoba-ku, Sendai 980-8579, Japan
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UENO Koichi
Department of Biochemical Pharmacology and Biotoxicology, Faculty of Pharmaceutical Sciences, Chiba University
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