HORMONAL-STIMULATION OF CA2- EVIDENCE FOR A CHANGE IN THE PARACELLULAR PATHWAY PERMEABILITY( AND MG2+ TRANSPORT IN THE CORTICAL THICK ASCENDING LIMB OF HENLES LOOP OF THE MOUSE )

Recent studies from our laboratory have shown that in the cortical thi ck ascending limb of Henle's loop of the mouse (cTAL) Ca2+ and Mg2+ ar e reabsorbed passively, via the paracellular shunt pathway. In the pre sent study, cellular mechanisms responsible for the hormone-stimulated Ca2+ and Mg2+ transport were investigated. Transepithelial voltages ( PD(te)) and transepithelial ion net fluxes (J(Na), J(Cl), J(K), J(Ca), J(Mg) were measured in isolated perfused mouse cTAL segments. Whether parathyroid hormone (PTH) is able to stimulate Ca2+ and Mg2+ reabsorp tion when active NaCl reabsorption, and thus PD(te), is abolished by l uminal furosemide was first tested. With symmetrical lumen and bath Ri nger's solutions, no Ca2+ and Mg2+ net transport was detectable, eithe r in the absence or in the presence of PTH. In the presence of luminal furosemide and a chemically imposed lumen-to-bath directed NaCl gradi ent, which generates a lumen-negative PD(te), PTH slightly but signifi cantly increased Ca2+ and Mg2+ net secretion. In the presence of lumin al furosemide and a chemically imposed bath-to-lumen-directed NaCl gra dient, which generates a lumen-positive PD(te), PTH slightly but signi ficantly increased Ca2+ and Mg2+ net reabsorption. In view of the obse rved small effect of PT on passive Ca2+ and Mg2+ movement, a possible interference of furosemide with the hormonal response was considered. To investigate this possibility, Ca2+ and Mg2+ transport vas first sti mulated with PTH in tubules under control conditions. Then active NaCl reabsorption was abolished by furosemide and the effect of PTH on J(C a) and J(Mg), measured. In the absence of PD(te) and under symmetrical conditions, no Ca2+ and Mg2+ transport was detectable, either in the presence or absence of PTH. In the presence of a bath-to-lumen-directe d NaCl gradient, Ca2+ and Mg2+ reabsorption was significantly higher i n the presence than in the absence of PTH. Finally, when active NaCL t ransport was not inhibited by furosemide, but reduced by a bath-to-lum en-directed NaCl gradient, PTH strongly increased J(Ca) and J(Mg), whe reas only a small increase in PD(te) was noted. In conclusion, these d ata suggest that PTH exerts a dual action on Ca2+ and Mg2+ transport i n the mouse cTAL by increasing the transepithelial driving force for C a2+ and Mg2+ reabsorption through hormone-mediated PD(te) alterations and by modifying the passive permeability for Ca2+ and Mg2+ of the epi thelium, very probably at the level of the paracellular shunt pathway.