Reference - Detail
| RRC ID | 17613 |
|---|---|
| Author | Kimura S, Nakagawa T, Matsuo Y, Ishida Y, Okamoto Y, Hayashi M. |
| Title | JTT-305, an orally active calcium-sensing receptor antagonist, stimulates transient parathyroid hormone release and bone formation in ovariectomized rats. |
| Journal | 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. |
| Volume | 668(1-2) |
| Pages | 331-6 |
| Published | 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 |
| Times Cited | 22 |
| WOS Category | PHARMACOLOGY & PHARMACY |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | COS-7(RCB0539) |