1998 Fiscal Year Final Research Report Summary
The mode of action, pharmacokinetics and mutual interaction of calcitonin and parathyroid hormone as the anti-osteoporotics
| Project/Area Number |
09470514
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | Setsunan University |
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Principal Investigator |
KOIDA Masao Setsunan University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (80039651)
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| Co-Investigator(Kenkyū-buntansha) |
KOHNO Takeyuki Setsunan University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 講師 (50178224)
NAKAMUTA Hiromichi Setsunan University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 講師 (70164275)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Calcitonin / Parathyroid hormone / Osteoporosis / Enzyme immunoassay / Osteoclast / Osteoblast / Bone resorption / Bone formation |
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| Research Abstract |
Of salmon calcitonin (sCT) and human parathyroid hormone (hPTH(1-34)) as the anti-osteoporotics, the mode of action, pharmacokinetics and possible mutual interaction were examined as follows. (1)Anti-osteoporotic action : Using ovariectomy (OVX)-and steroid-induced models of osteoporosis, the dose-response relationship were estimated histomorphometrically and biomechanically and the equipotent doses for sCT and hPTH(1-34) to produce 60 to 65% recovery in bone structure within 8weeks were 20U/kg, s. c. /5days/week and 10 ug/kgs.c/5days/ week, respectively.(2)Pharmacokinetic and interaction : The ultra-sensitive ELISAs for sCT, hPTH(1 -34), rat PTH and rat osteocalcin were developed and applied for the pharmacokinetic study in which sCT-induced changes in the blood level of endogenous PTH was followed to search for the possible participation of PTH in the anti-osteoporotic action of sCT, with a positive result indicating the participation to some extent. (3)Mechanism of action and new fi
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nding I : The in vitro action ofhPTH(1-34) on osteoclast (OC) and osteoblast (0B) which are mainly in charge of bone metabolism were examined. hPTH(1-34) strongly stimnulated the pit-forming activity of OC but with a concomitant fall (1/16) in the sensitivity toward the anti-resorbing effect of sCT and by comparing the reactivities toward some cytokines, the cell function was characterized. A nodule-forming system using 0B from bone marrow of new-born rats was established and using the in vitro system it was attempted to reproduce the in vivo bone anabolic action of hPTH(1-34), but the nodule formation was consistently suppressed by hPTH(1-34). An unexpected finding was that FCS used for culture possibly contained both inhibitory and stimulatory factors for nodule formation and a study for identifing those factors is underway. (4)New finding Ii : Adult female rats showed no detectable daily rhythm in the urinary excretion pattern of deoxypyridinoline(D-Pyr), a clinical indicator of bone resorption(rise in osteoporotic diseases) but after OVXa daily rhythm of low in light and high in dark ensued. In such ovariectomized rats, an anti-osteoporotic dose of sCT increased the excretion while it decreased the blood level. Studies on the mechanism of sCT-increased excretion and on the reliablity of urinary D-Pyr as the resorption indicator are in progress. Less
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