Effects of glucagon on Na⁺, Cl⁻, K⁺, Mg²⁺ and Ca²⁺ transports in cortical and medullary thick ascending limbs of mouse kidney

Abstract

The effects of glucagon on transepithelial Na⁺, Cl⁻, K⁺, Ca²⁺ and Mg²⁺ net fluxes were investigated in isolated perfused cortical (cTAL) and medullary (mTAL) thick ascending limbs of Henle's loop of the mouse nephron. Transepithelial ion net fluxes (J _Na ⁺,J _Cl ⁻,J _K ⁺,J _Ca ²⁺,J _Mg ²⁺) were determined by electron probe analysis of the collected tubular fluid. Simultaneously the transepithelial voltage (PD_te) and the transepithelial resistance (R _te) were recorded. In cTAL-segments (n=8), glucagon (1.2×10⁻⁸ mol · l⁻¹) stimulated significantly the reabsorption of Na⁺, Cl⁻, Ca²⁺ and Mg²⁺∶J _Na ⁺ increased from 204±20 to 228±23 pmol · min⁻¹ · mm⁻¹,J _Cl ⁻ from 203±18 to 234±21 pmol · min⁻¹ · mm⁻¹,J _Ca ²⁺ from 0.52±0.13 to 1.34±0.30 pmol · min⁻¹ · mm⁻¹ andJ _Mg ²⁺ from 0.51±0.08 to 0.84±0.08 pmol · min⁻¹ · mm⁻¹.J _K+ remained unchanged: 3.2±1.3 versus 4.0±1.9 pmol · min⁻¹ · mm⁻¹. Neither PD_te (16.3±1.5 versus 15.9±1.4 mV) norR _te (22.5±3.0 versus 20.3±2.6 Ωcm²) were changed significantly by glucagon. However, in the post-experimental periods a significant decrease in PD_te and increase inR _te were noted. In mTAL-segments (n=9), Mg²⁺ and Ca²⁺ transports were close to zero and glucagon elicited no significant effect. The reabsorptions of Na⁺ and Cl⁻, however, were strongly stimulated:J _Na ⁺ increased from 153±17 to 226±30 pmol · min⁻¹ · mm⁻¹ andJ _Cl ⁻ from 151±23 to 243±30 pmol · min⁻¹ · mm⁻¹. The rise in NaCl transport was accompanied by an increase in PD_te from 10.3±1.1 to 12.3±1.2 mV and a decrease inR _te from 19.1±2.7 to 17.8±2.0 Ωcm². No net K⁺ movement was detectable either in the absence or in the presence of glucagon. A micropuncture study carried out in hormone-deprived rats indicated that glucagon stimulates Na⁺, Cl⁻, K⁺, Mg²⁺ and Ca²⁺ reabsorptions in the loop of Henle. In conclusion our data demonstrate that glucagon stimulates NaCl reabsorption in the mTAL segment and to a lesser extent in the cTAL segment whereas it stimulates Ca²⁺ and Mg²⁺ reabsorptions only in the cortical part of the thick ascending limb of the mouse nephron. These data are in good agreement with, and extend, those obtained in vivo on the rat with the hormone-deprived model.