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.
Gesek
F A
FA
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755.
Friedman
P A
PA
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002116:Calcitonin / Q000494:pharmacology*; D002118:Calcium / Q000493:pharmacokinetics*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007686:Kidney Tubules, Distal / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000494:pharmacology; D013997:Time Factors
D015220:Calcium Channels; D004095:Dihydropyridines; D010281:Parathyroid Hormone; C038806:1,4-dihydropyridine; D002116:Calcitonin; D003513:Cycloheximide; D009543:Nifedipine; D002118:Calcium