INSULIN STIMULATES NA(-), CA-2+, AND MG-2+ TRANSPORTS IN TAL OF MOUSENEPHRON - CROSS-POTENTIATION WITH AVP(), CL()

Insulin (Ins) decreases Na+ delivery in the final urine. To determine whether the loop of Henle participates in this reduction, the effects of Ins were tested on cortical (CTAL) and medullary thick ascending li mbs (MTAL) of the mouse nephron, microperfused in vitro. In the MTAL, Ins increased the transepithelial potential difference (V(t)) and the Na+ and Cl- net reabsorption fluxes (J(Na) and J(Cl), respectively) in a dose-dependent manner, the threshold being below 10(-9) M. At 10(-7 ) M, Ins reversibly increased J(Na) and J(Cl), leaving Mg2+ and Ca2+ f luxes (J(Mg) and J(Ca), respectively) close to zero. In the CTAL, 10(- 7) M Ins reversibly increased V(t), J(Na), J(Cl), J(Mg), and J(Ca). In CTAL segments perfused under asymmetrical conditions, with a bath-to- lumen-directed NaCl gradient (lumen 50 mM NaCl, bath 150 mM NaCl), add ition of 10(-7) M Ins to the bath resulted in a large increase in J(Mg ) and J(Ca). Thus the responses of CTAL and MTAL to Ins are in all way s similar to those already reported for the adenosine 3',5'-cyclic mon ophosphate (cAMP)-generating hormones acting on these nephron segments . When 10(-10) M arginine vasopressin (AVP) and 10(-7) M Ins were used in combination, previous addition of one hormone to the bath potentia ted the response to the second hormone. In cAMP accumulation experimen ts, performed in the presence of a phosphodiesterase inhibitor, the, a mounts of cAMP formed with 10(-7) M Ins and 10(-10) M AVP (which elici t maximal physiological responses in these segments) were in the same range. The combined effect of Ins and AVP on cAMP accumulation was hig her than the effect of either hormone used alone. In conclusion, 1) In s directly stimulates NaCl, Ca2+, and Mg2+ transports in the mouse TAL ; 2) the similarity of the effects of Ins and AVP may be due to their ability to generate intracellular cAMP; and 3) there is a cross-potent iation between the effects of Ins and AVP in this nephron segment.