Calcitonin stimulates calcium transport in distal convoluted tubule cells.

Calcitonin increases Ca2+ absorption by renal distal tubules. The mechanism underlying this action is not known. Calcitonin effects on Ca2+ uptake, intracellular Ca2+ activity, and membrane voltage were determined in transformed mouse distal convoluted tubule (DCT) cells. Intracellular Ca2+, measured in single cells grown on cover slips and loaded with fura-2, averaged 102 nM. Maximal increases of intracellular Ca2+ to 312 nM were elicited by 1 nM calcitonin. Calcitonin stimulated 45Ca2+ influx by 45% from control rates of 2.8 nmol.min-1 x mg protein-1. Membrane voltage was measured in single cells loaded with the voltage-sensitive dye 3,3'-dihexyloxacarbocyanine iodide. Resting membrane voltage averaged 69 mV. Calcitonin maximally hyperpolarized cells by 18 mV. The Cl- channel blocker, 5-nitro-2-(3-phenylpropylamino)benzoic acid, abolished calcitonin-induced membrane hyperpolarization and Ca2+ influx. Calcitonin increased halide ion permeability, estimated from the rate of 125I- efflux, by 160%. The Ca2+ channel blocker nifedipine abolished calcitonin-stimulated 45Ca2+ uptake and the increase of intracellular Ca2+. Combined exposure to calcitonin and parathyroid hormone (PTH) had no additional effect on 45Ca2+ influx or intracellular Ca2+. In contrast to the long latency (8 min) before onset of PTH effects, calcitonin increased 45Ca2+ uptake and intracellular Ca2+ concentration within 2 min. Blockade of protein synthesis with cycloheximide inhibited Ca2+ uptake induced by PTH but not that stimulated by calcitonin. We conclude that calcitonin increases Cl- conductance in DCT cells, resulting in membrane hyperpolarization and activation of Ca2+ entry through dihydropyridine-sensitive Ca2+ channels. The shorter onset of calcitonin action compared with PTH may reflect differences in the signaling mechanisms between the two hormones.