Effects of PTH, ADH, and cyclic AMP on distal tubular Ca and Na reabsorption

Abstract

Tubular microperfusion experiments were performed in rats to examine the effects of thyroparathyroidectomy (TPTX), parathyroid hormone (PTH), antidiuretic hormone (ADH), and cyclic AMP (cAMP) on distal tubular Ca, Na, and water reabsorption. TPTX caused a significant decrease in the Ca reabsorptive rate as compared to intact animals. PTH (5 U/kg; 2 U x kg-1 x h-1) replacement in TPTX animals restored Ca transport to control levels. Application of either cAMP (10(-3) M) or 8-(p-chlorophenylthio)-cyclic 3',5'-adenosine monophosphate (10(-5) M) to the surface of the kidney caused a stimulation of Ca reabsorption similar to that produced by PTH. Neither TPTX nor PTH changed Na or water reabsorption significantly, whereas the cyclic nucleotides increased both of these parameters. These later actions of cAMP duplicated effects of ADH observed in these distal tubules.

On the mechanism of parathyroid hormone stimulation of calcium uptake by mouse distal convoluted tubule cells.

“…We also measured 22Na+ uptake at 1, 2, and 5 min after addition of 10 -8 M PTH but found no effect compared to untreated controls. Comparable observations have been made during in vivo and in vitro distal convoluted tubule microperfusion experiments where PTH increased calcium but not sodium absorption (12,34,38). Furthermore, increased sodium entry would be expected to depolarize distal convoluted tubule cells.…”

“…However, certain physiological, pharmacological, or pathological influences are known to dissociate one from the other. PTH, for instance, reduces renal calcium exere-tion without a change in sodium excretion (10,12,38). Although the mechanisms responsible for the dissociation are not known definitively, they all proceed in distal convoluted tubules.…”

“…The major sites at which PTH stimulates renal calcium absorption are cortical thick ascending limbs of Henle's loop (1)(2)(3)(4), distal convoluted tubules (5,6) or, in the rabbit, in connecting tubules (7)(8)(9). In these hormone-sensitive nephron segments, PTH increases active, transcellular calcium trans-port (3, [10][11][12]. PTH-induced increases in calcium absorption are associated with a rise of intracellular calcium activity ([Ca2+]i)' in cortical thick ascending limbs ( 13) and in connecting tubules (7).…”

Mechanism of calcium transport stimulated by chlorothiazide in mouse distal convoluted tubule cells.

“…We recently demonstrated that parathyroid hormone stimulates calcium entry in primary cell cultures ofcortical thick ascending limb and distal convoluted tubule cells by activating dihydropyridine-sensitive calcium channels (16). Activation of such dihydropyridine-sensitive calcium channels in apical plasma membranes is consistent with the physiological effect ofparathyroid hormone to increase the rate oftransepithelial calcium transport ( 17,18). Taken together, these observations suggested a plausible mechanism by which thiazide diuretics might stimulate calcium transport.…”

Inducible nitric oxide synthase expression is reduced in cystic fibrosis murine and human airway epithelial cells.

“…Although there is evidence for a physical interaction, these data do not explain all the phenomena associated with ENaC. For example, amiloride-sensitive sodium transport is stimulated by cAMP in renal distal tubules, even though these cells express both CFTR and ENaC (5,6). An alternative possibility is that the loss of some cellular signal in CF airway epithelia that normally serves to down-regulate sodium absorption may play a role in initiating the increased rate of sodium absorption.…”