ArticleThe Journal of clinical investigation2000
Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 275 citations in OpenAlex.
- PTH-Independent CaSR Inhibition with the Oral Calcilytic Encaleret Improves Calcium Homeostasis in Post-Surgical Hypoparathyroidism: A Phase 2 Open-Label Proof-of-Concept Trial.Research square · 2026Article
- G protein-coupled receptor signaling in osteogenic bone mesenchymal stem/stromal cells.Frontiers in cell and developmental biology · 2026Review
- Activation of CaExperimental brain research · 2025Article
- A novel chemoreactive calcilytic for the potential treatment of autosomal dominant hypocalcemia.Acta pharmaceutica Sinica. B · 2025Article
- Chiral Supramolecular Hydrogels Regulating Both Osteoblastogenesis and Osteoclastogenesis.Gels (Basel, Switzerland) · 2025Article
- Ophthalmate is a new regulator of motor functions via CaSR: implications for movement disorders.Brain : a journal of neurology · 2024Article
- Glutathione-Based Photoaffinity Probe Identifies Caffeine as a Positive Allosteric Modulator of the Calcium-Sensing Receptor.ACS chemical biology · 2024Article
- An LGR4 agonist activates the GSK‑3β pathway to inhibit RANK‑RANKL signaling during osteoclastogenesis in bone marrow‑derived macrophages.International journal of molecular medicine · 2024Article
- The bromodomain inhibitor JQ1+ reduces calcium-sensing receptor activity in pituitary cell lines.Journal of molecular endocrinology · 2021Article
- Therapeutic Opportunities of Targeting Allosteric Binding Sites on the Calcium-Sensing Receptor.ACS pharmacology & translational science · 2021Review
- Old and New Drugs for the Management of Bone Disorders in CKD.Calcified tissue international · 2021Review
- Aberrant upregulation of CaSR promotes pathological new bone formation in ankylosing spondylitis.EMBO molecular medicine · 2020Article
- Calhex231 ameliorates myocardial fibrosis post myocardial infarction in rats through the autophagy-NLRP3 inflammasome pathway in macrophages.Journal of cellular and molecular medicine · 2020Article
- Calcilytic NPSP795 Increases Plasma Calcium and PTH in an Autosomal Dominant Hypocalcemia Type 1 Mouse Model.JBMR plus · 2020Article
- Illuminating the allosteric modulation of the calcium-sensing receptor.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- International Union of Basic and Clinical Pharmacology. CVIII. Calcium-Sensing Receptor Nomenclature, Pharmacology, and Function.Pharmacological reviews · 2020Review
- Negative allosteric modulators of the human calcium-sensing receptor bind to overlapping and distinct sites within the 7-transmembrane domain.British journal of pharmacology · 2020Article
- G Protein-Coupled Receptors in Taste Physiology and Pharmacology.Frontiers in pharmacology · 2020Review
- The CaSR in Pathogenesis of Breast Cancer: A New Target for Early Stage Bone Metastases.Frontiers in oncology · 2020Review
- Dual Action Calcium-Sensing Receptor Modulator Unmasks Novel Mode-Switching Mechanism.ACS pharmacology & translational science · 2018Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a "calcilytic") of the parathyroid cell Ca(2+) receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17beta-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca(2+) receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.