Calcium-sensing receptor signaling pathways in medullary thick ascending limb cells mediate COX-2-derived PGE2 production: functional significance

摘要

the calcium-sensing receptor (CaR) expressed in the cortical and medullary thick ascending limb (mTAL), distal convoluted tubule, macula densa, inner medullary collecting duct, and proximal tubule (PT) (14,49, 50, 64) signals through Gq and G_i pathways to regulate Ca~(2+) homeostasis and modulates Na+, Cl , Ca~(2+), and H2O transport in the kidney (8, 9). Activation of the CaR, expressed on the basolateral membranes of the TAL, inhibits salt transport in a furosemide-like manner (7, 27). The CaR is also expressed by primary cultures of mTAL cells, mediating increases of tumor necrosis factor (TNF) production and cyclooxygenase-2 (COX-2) expression as well as prostaglandin E2 (PGE2) synthesis thereby contributing to a mechanism that regulates NaCl reabsorption in this nephron segment (55-57).