AJP - Renal Physiology, Vol 264, Issue 4 744-F751, Copyright © 1993 by American Physiological Society

ARTICLES

Calcitonin stimulates calcium transport in distal convoluted tubule cells

F. A. Gesek and P. A. Friedman
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755.

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.

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