Funding outcome

Calcium is vital to appropriate skeletal growth and multiple functions in the body. Thus the amount in blood is tightly regulated. The mechanism by which the body detects blood calcium levels is via a calcium-sensing receptor (CaSR) which is expressed on the surface of some cells facing the blood including n the intestine. The CaSR detects high blood calcium levels and singles events to lower blood calcium by inhibiting the secretion of parathyroid hormone and also by directly increasing excretion of calcium in the urine. Though present along the intestinal tract, the function of the CaSR in maintaining blood calcium levels is not known. We hypothesize that the CaSR detects blood calcium levels and signals to stop intestinal calcium absorption. To test our hypothesis, we will use radioactive calcium to measure calcium movement directly across intestinal sections from mice. This enables us to expose the tissue to CaSR activators (i.e. impose a high calcium state) and directly measure its effect on calcium absorption. Our preliminary results suggest that CaSR activation indeed decreases intestinal calcium absorption. We will further investigate this by delineating the underlying molecular mechanisms of how CaSR inhibits intestinal calcium absorption with genetically modified mice and pharmacological inhibitors. Given the lack of understanding of the role of the CaSR in calcium absorption, our study will provide fundamental knowledge, which can be used by scientists and clinicians to inform how much calcium should be consumed and to treat calcium disorders such as osteoporosis and kidney stones.