Short-term effects of thyroid hormones on the Na/H antiport in L-6 myoblasts: High molecular specificity for 3,3 ',5-triiodo-L-thyronine

The thyroid hormones L-T-3 and L-T-4 were shown to activate the Na/H antipo rt in L-6 cells from rat skeletal muscle by a rapid, nongenomic mechanism. Under pH equilibrium conditions, a significant rise in the intracellular pH , measured by the fluorescent pH indicator 2',7'-bis-(carboxyethyl)-5(6)-ca rboxyfluorescein was observed after the addition of physiological concentra tions (10(-10) M) of either L-T-3 or L-T-4, but with different time courses . L-T-3 at all concentrations increased the pH after a delay of 2 min, wher eas L-T-4 showed a concentration-dependent lag time, going from 11 min at 1 0(-11) M down to 5 min for a hormone concentration of 10(-6) M. The effect of L-T-4 was blocked in the presence of the 5'-deiodinase inhibitor 6-n-pro pyl-2-thiouracil, suggesting that the difference in lag time between L-T-3 and L-T-4 was due to the 5'-deiodination process that transforms L-T-4 into the bioactive L-T-3. In short term studies (<5 min), a high molecular spec ificity for L-T-3 was found, as L-T-4, rT(3), the D-isomer of T-3, and the deaminated analogues were ineffective at physiological concentrations. In a nalogy with the results found at equilibrium, intracellular pH recovery fro m an acid load and set-point were increased after 2 min for L-T-3 (10(-9) M ) and after 10 min for L-T-4 (10(-9) M). The effect of the hormones on the intracellular pH was completely blocked by the specific antiport inhibitor 5-(ethyl-N-isopropyl)amiloride. These findings suggest that thyroid hormone s may play an active role in the recovery from muscular acidosis through di rect stimulation of the Na/H antiport.