| RRC ID |
17613
|
| 著者 |
Kimura S, Nakagawa T, Matsuo Y, Ishida Y, Okamoto Y, Hayashi M.
|
| タイトル |
JTT-305, an orally active calcium-sensing receptor antagonist, stimulates transient parathyroid hormone release and bone formation in ovariectomized rats.
|
| ジャーナル |
Eur J Pharmacol
|
| Abstract |
Intermittent administration of parathyroid hormone (PTH) has a potent anabolic effect on bone in humans and animals. Calcium-sensing receptor (CaSR) antagonists stimulate endogenous PTH secretion through CaSR on the surface of parathyroid cells and thereby may be anabolic agents for osteoporosis. JTT-305 is a potent oral short-acting CaSR antagonist and transiently stimulates endogenous PTH secretion. The objective of the present study was to investigate the effects of JTT-305 on PTH secretion and bone in ovariectomized rats. Female rats, immediately after ovariectomy (OVX), were orally administered vehicle or JTT-305 (0.3, 1, or 3 mg/kg) for 12 weeks. The serum PTH concentrations were transiently elevated with increasing doses of JTT-305. In the proximal tibia, JTT-305 prevented OVX-induced decreases in both the cancellous and total bone mineral density (BMD) except for the 0.3mg/kg dose. At the 3mg/kg dose, JTT-305 increased the mineralizing surface and bone formation rate in histomorphometry. The efficacy of JTT-305 at the 3mg/kg dose on the BMD corresponded to that of exogenous rat PTH1-84 injection at doses between 3 and 10 μg/kg. In conclusion, JTT-305 stimulated endogenous transient PTH secretion and bone formation, and consequently prevented bone loss in OVX rats. These results suggest that JTT-305 is orally active and has the potential to be an anabolic agent for the treatment of osteoporosis.
|
| 巻・号 |
668(1-2)
|
| ページ |
331-6
|
| 公開日 |
2011-10-1
|
| DOI |
10.1016/j.ejphar.2011.07.015
|
| PII |
S0014-2999(11)00790-4
|
| PMID |
21810422
|
| MeSH |
Administration, Oral
Animals
Benzoates / administration & dosage
Benzoates / pharmacokinetics
Benzoates / pharmacology*
COS Cells
Chlorocebus aethiops
Female
Humans
Osteogenesis / drug effects*
Ovariectomy*
Parathyroid Hormone / metabolism*
Propanolamines / administration & dosage
Propanolamines / pharmacokinetics
Propanolamines / pharmacology*
Rats
Rats, Sprague-Dawley
Receptors, Calcium-Sensing / antagonists & inhibitors*
Receptors, Calcium-Sensing / metabolism
Recombinant Proteins / pharmacology
|
| IF |
3.263
|
| 引用数 |
22
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
| リソース情報 |
| ヒト・動物細胞 |
COS-7(RCB0539) |
