Effect of parathyroid hormone on the connecting tubule from the rabbit kidney: biphasic response of transmural voltage |
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Authors: | Toshikatsu Shimizu Koji Yoshitomi Masuhisa Nakamura Masashi Imai |
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Institution: | (1) Shionogi Research Laboratories, Shionogi & Co. Ltd, 553 Osaka, Japan;(2) Department of Pharmacology, Jichi Medical School, Minami Kawachi, Kawachi, 329-04 Tochigi, Japan |
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Abstract: | The effect of parathyroid hormone (PTH) on ion transport was examined by observing transmural (V
T) and basolateral membrane voltage (V
B) in the in vitro perfused rabbit connecting tubule. Addition of 10 nmol/l PTH to the bath induced a biphasic response of V
T, with hyperpolarization followed by depolarization. Chlorophenylthioadenosine cyclic 3,5-monophosphate mimicked the effect of PTH, which did not change the V
B in the connecting tubule cell, but mainly caused changes in the apical membrane voltage. The V
T of distal convoluted tubule and the cortical collecting duct were not affected by PTH. Elimination of Na+ from the lumen abolished the PTH-induced V
T responses in the connecting tubule. In the presence of 10 mol/l amiloride, PTH caused an initial hyperpolarization but did not induce the late depolarization. The same was seen in the absence of luminal Ca2+. Either addition of 0.1 mmol/l ouabain to the bath or elimination of bath Na+ completely abolished the PTH-induced V
T changes. The presence of 5 mmol/l Ba2+ in the lumen did not affect the response to PTH. These findings indicate that the initial hyperpolarization may be caused by an increase in Na+ influx across the luminal membrane through an amiloride-insensitive Na+ conductive pathway and that the late depolarization may be caused by the decrease in Na+ influx through the amiloride-sensitive Na+ conductive pathway. Luminal Ca2+ is necessary for the late depolarization caused by PTH. On the basis of these observations, we suggest that PTH initially increase influxes of both Na+ and Ca2+ across the luminal membrane and that an increase in intracellular Ca2+ in turn suppresses Na+ entry through the luminal amiloride-sensitive Na+ channel. |
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Keywords: | Parathyroid hormone Na+ conductance Amiloride Ca2+ |
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