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Monitoring ER/SR Calcium Release with the Targeted Ca2+ Sensor CatchER+
Published on: May 19, 2017
The calcium-sensing receptor: physiology, pathophysiology and CaR-based therapeutics
1Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. embrown@partner.org
Sub-Cellular Biochemistry
|January 16, 2008
Summary
The calcium-sensing receptor (CaR) regulates blood calcium levels. Mutations in CaR cause disorders like hypercalcemia or hypocalcemia, while drugs targeting CaR offer new treatments for related conditions.
Area of Science:
- Endocrinology
- Molecular Biology
- Nephrology
Background:
- The calcium-sensing receptor (CaR) is crucial for maintaining calcium homeostasis.
- CaR is expressed in parathyroid glands and kidneys, regulating calcium and water metabolism.
- Disruptions in CaR function lead to various calcium disorders.
Purpose of the Study:
- To summarize the role of the CaR in calcium homeostasis.
- To describe CaR-related disorders caused by genetic mutations or antibodies.
- To introduce CaR-targeting drugs (calcimimetics and calcilytics) and their therapeutic potential.
Main Methods:
- Review of literature on CaR function, genetics, and pharmacology.
- Analysis of clinical manifestations of CaR-related disorders.
- Discussion of current and potential therapeutic applications of CaR modulators.
Main Results:
- Inactivating CaR mutations cause Familial Hypocalciuric Hypercalcemia (FHH) and Neonatal Severe Hyperparathyroidism (NSHPT).
- Activating CaR mutations lead to autosomal dominant hypocalcemia.
- Antibodies against CaR can mimic these genetic disorders.
- Calcimimetics manage hyperparathyroidism in dialysis and parathyroid cancer patients.
- Calcilytics are explored for osteoporosis treatment by mimicking parathyroid hormone pulses.
Conclusions:
- The CaR is a vital regulator of calcium balance, with its dysfunction leading to significant clinical syndromes.
- Pharmacological targeting of CaR with calcimimetics and calcilytics offers promising therapeutic strategies for diverse conditions.
- Further research into CaR modulation holds potential for novel treatments in metabolic bone diseases and endocrine disorders.
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