Localization and function of the renal calcium-sensing receptor

The ability to monitor changes in the ionic composition of the extracellular environment is a crucial feature that has evolved in all living organisms. The cloning and characterization of the extracellular calcium-sensing receptor (CaSR) from the mammalian parathyroid gland in the early 1990s provided the first description of a cellular, ion-sensing mechanism. This finding demonstrated how cells can detect small, physiological variations in free ionized calcium (Ca 2+) in the extracellular fluid and subsequently evoke an appropriate biological response by altering the secretion of parathyroid hormone (PTH) that acts on PTH receptors expressed in target tissues, including the kidney, intestine, and bone. Aberrant Ca 2+ sensing by the parathyroid glands, as a result of altered CaSR expression or function, is associated with impaired divalent cation homeostasis. CaSR activators that mimic the effects of Ca 2+ (calcimimetics) have been designed to treat hyperparathyroidism, and CaSR antagonists (calcilytics) are in development for the treatment of hypercalciuric disorders. The kidney expresses a CaSR that might directly contribute to the regulation of many aspects of renal function in a PTH-independent manner. This Review discusses the roles of the renal CaSR and the potential impact of pharmacological modulation of the CaSR on renal function

Proximate and Sensory Evaluation of Fermented Seasonings from Soybean and Fluted Pumpkin Seeds

Specialty condiment (ogiri) was produced from seeds of soybean (Glycine max) and fluted pumpkin (Telfairia occidentalis) by spontaneous moist solid substrate fermentation of their pre-processed mash. The two samples coded FSBM and FFPM respectively were evaluated for nutritional quality. Effects of fermentation on proximate values of the seeds were also analyzed. The two samples were further subjected to sensory analysis using commercial brand made  from castor bean (Ricinus communis) seeds coded FCBM as a control. Results show that FFPM was significantly (p < 0.05) higher in ash, crude fiber and protein, but significantly lower in moisture and fat than the FSBM. There was no significant (p > 0.05) difference in carbohydrate content of the two samples. The FFPM recorded significant (p < 0.05) increase in crude fiber, fat and protein, and significant (p < 0.05) decrease in moisture, ash and carbohydrate compared to the values in the fluted pumpkin seeds. The FSBM recorded significant (p < 0.05) rise in fat and protein, but significant drop in moisture, ash, crude fiber and carbohydrate compared to the values in soybean seeds. Sensory results show that FFPM was significantly (p < 0.05) higher than FSBM in flavor and marginally (p > 0.05) different in color, texture, taste and general acceptability. Baring the marginal (p < 0.05) superiority in taste, the FCBM was significantly (p<0.05) lower in every other attributes considered. It follows that good quality fermented condiments can be obtained from cheaper and underutilized oil seeds

The calcium-sensing receptor (CaSR) defends against hypercalcemia independently of its regulation of parathyroid hormone secretion

The calcium-sensing receptor (CaSR) controls parathyroid hormone (PTH) secretion, which, in turn, via direct and indirect actions on kidney, bone, and intestine, maintains a normal extracellular ionized calcium concentration (Ca2+o). There is less understanding of the CaSR's homeostatic importance outside of the parathyroid gland. We have employed single and double knockout mouse models, namely mice lacking PTH alone (CaSR+/+ PTH−/−, referred to as C+P−), lacking both CaSR and PTH (CaSR−/− PTH−/−, C−P−) or wild-type (CaSR+/+ PTH+/+, C+P+) mice to study CaSR-specific functions without confounding CaSR-mediated changes in PTH. The mice received three hypercalcemic challenges: an oral Ca2+ load, injection or constant infusion of PTH via osmotic pump, or a phosphate-deficient diet. C−P− mice show increased susceptibility to developing hypercalcemia with all three challenges compared with the other two genotypes, whereas C+P− mice defend against hypercalcemia similarly to C+P+ mice. Reduced renal Ca2+ clearance contributes to the intolerance of the C−P− mice to Ca2+ loads, as they excrete less Ca2+ at any given Ca2+o than the other two genotypes, confirming the CaSR's direct role in regulating renal Ca2+ handling. In addition, C+P+ and C+P−, but not C−P−, mice showed increases in serum calcitonin (CT) levels during hypercalcemia. The level of 1,25(OH)2D3 in C−P− mice, in contrast, was similar to those in C+P− and C+P+ mice during an oral Ca2+ load, indicating that increased 1,25(OH)2D3 production cannot account for the oral Ca2+-induced hypercalcemia in the C−P− mice. Thus, CaSR-stimulated PTH release serves as a “floor” to defend against hypocalcemia. In contrast, high-Ca2+o-induced inhibition of PTH is not required for a robust defense against hypercalcemia, at least in mice, whereas high-Ca2+o-stimulated, CaSR-mediated CT secretion and renal Ca2+ excretion, and perhaps other factors, serve as a “ceiling” to limit hypercalcemia resulting from various types of hypercalcemic challenges