Kidney and Calcitonin

The adenylate cyclase [ATP pyrophosphatelyase (cyclizing), EC 4.6.1.1] sensitivity to salmon calcitonin in 11 different segments of the rabbit nephron was investigated using a micromethod for enzyme activity measurements in samples, each containing a single piece of tubule. The required segments were isolated by microdissection from collagenasetreated rabbit kidneys. The results were expressed as femtomoles of adenosine 3':5'-cyclic monophosphate formed per mm of tubular length per 30 min of incubation time. In the presence of 0.1 gg/ml of synthetic salmon calcitonin, it was found that eight segments exhibited no hormonal sensitivity whereas maximal responses were induced in three segments, the "bright" portion of the distal convoluted tubule, the cortical and the medullary portions of the thick ascending limb of the loop of Henle (stimulated over control activity ratios were 32, 11, and 27). The very high sensitivity to calcitonin of the adenylate cyclase contained in these three segments (0.01 ng/ml of salmon calcitonin inducing a 2-fold stimulation; half-maximal stimulation corresponding to about 0.3 ng/ml of salmon calcitonin) suggests that the distal convoluted tubule, as well as the cortical and medullary portions of the thick ascending limb of the loop of Henle represent physiological target structures of calcitonin action within the kidney.It has been shown several times that calcitonin is able to stimulate adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6

show abstract

“…It (22)(23)(24), the magnitude of which depends on experimental conditions, animal species and the origin of the hormonal preparation used.…”

Section: Discussionmentioning

confidence: 99%

Distribution of calcitonin-sensitive adenylate cyclase activity along the rabbit kidney tubule.

Chabardès¹,

Imbert–Teboul²,

Montegut³

et al. 1976

Proc. Natl. Acad. Sci. U.S.A.

100

View full text Add to dashboard Cite

show abstract

“…Calcitonin is a polypeptide hormone that causes hypocalcemia by means of inhibition of the release of calcium from bone and stimulation of urinary calcium excretion (1,2). The initial step of the action of calcitonin is binding to receptors on plasma membranes of renal and bone cells (3).…”

mentioning

confidence: 99%

Calcitonin and calcium ionophores: cyclic AMP responses in cells of a human lymphoid line.

Moran¹,

Hunziker²,

Fischer³

1978

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Receptors for calcitonin, as assayed by the specific binding of 'SI-labeled salmon calcitonin and stimulation of cyclic AMP formation, were found in 886 cels derived from a human lymphoid line. The affinity of calcitonin from different species and of various analogues of human calcitonin for the binding sites and their ability to stimulate cyclic AMP formation were closely related to their hypocalcemic activity and presumably reflected biological properties of the hormones. Cell Culture, Isolation, and Incubation. The 8866 cells were derived from a patient with chronic myelogeneous leukemia (6) and were generously provided by S. J. Marx (NIAMDD). They were cultured in RPMI 1640 medium with 2 mM L-glutamine, supplemented with 10% fetal calf serum (vol/vol; Gibco, Glasgow, Scotland) and 0.5 ,ug of neomycin sulfate per ml, under a humid atmosphere of 95% air/5% CO2 at 370. Cells were fed two to three times weekly by 1:3 dilution in fresh growth medium. The cells were harvested at the late phase of exponential growth by sedimentation for 10 min at 300 X g at 40, washed three times in the incubation medium, and resuspended to a density of 107 cells per ml.The incubation medium contained 25 mM The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

show abstract

“…(iii) The Na pump is independently inhibited via the PKC pathway. These results demonstrate a direct link between CT and Na transport in a proximal kidney tubule cell line, a response possibly related to the potent natriuretic effect of the hormone in vivo (2,3).…”

Section: Discussionmentioning

confidence: 59%

“…Calcitonin (CT), a 32-amino acid hormone with profound hypocalcemic effects due to its action in bone and the kidney (1,2), also increases urinary excretion of Na (3). The mechanisms underlying this effect of CT on the kidney tubule, however, have not been elucidated.…”

mentioning

confidence: 99%

Cell cycle-dependent and kinase-specific regulation of the apical Na/H exchanger and the Na,K-ATPase in the kidney cell line LLC-PK1 by calcitonin.

Chakraborty

Chatterjee²,

Gorelick³

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Calcitonin (CT), which regulates serum calcium through its actions in bone and the kidney tubule, also has a potent natriuretic effect in vivo. Na reabsorption in the proximal kidney tubule is mostly dependent on the activity of the Na,K-ATPase and the apical Na/H exchanger. We have previously shown that CT regulates the activity of the Na,KATPase in the proximal kidney tubule cell line LLC-PKj in a cell cycle-dependent manner. We report here that, in the same cells, CT also regulates the Na/H exchanger through a cell cycle-specific activation of the Ca/calmodulin-dependent protein kinase II. In G2 phase, no changes in ethylisopropyl amiloride-sensitive 22Na uptake is observed, despite an increase in cAMP. In contrast, the hormone inhibits the apical exchanger when the cells are in S phase, resulting in an 80% inhibition of 22Na uptake. These results demonstrate that CT affects the activity of the two major proximal tubule Na transport systems and may help clarify the mechanisms by which CT regulates Na+ reabsorption.Calcitonin (CT), a 32-amino acid hormone with profound hypocalcemic effects due to its action in bone and the kidney (1, 2), also increases urinary excretion of Na (3). The mechanisms underlying this effect of CT on the kidney tubule, however, have not been elucidated. In the kidney, Na reabsorption results mostly from activity of the basolateral Na,K-ATPase and the apical Na/H exchanger (NHE) in the proximal tubule and/or Na channels in the distal tubule (4, 5). We have reported (6) that CT regulates Na,K-ATPase in a proximal kidney tubule cell line (LLC-PK1) (7), with the effect of the hormone depending on the position of the cells in the cell cycle; during G2, CT increases cAMP via the stimulatory guanine nucleotide-binding protein (G, protein) (8)(9)(10). The second NHE isoform is found in the apical membrane domain of renal, intestinal, and gall bladder epithelia (10). This apical NHE is less sensitive to inhibition by amiloride and is primarily involved in Na+ reabsorption and proton secretion. A third isoform has recently been reported in the intestine (11) but it is not yet well characterized.CT activates several signal transduction pathways (6, 12-14), some differentially along the kidney tubule (15, 16), which could affect the activity of the NHEs (17). The major objective of this study was therefore to determine whether CT regulates the NHEs in LLC-PK1 cells, whether such effects varied with the phase of the cell cycle, and how the observed responses, if any, could be related to the changes in Na,K-ATPase activity and the natriuretic effect of the hormone.MATERIALS AND METHODS Materials. Salmon calcitonin was from Rorer Central Research (King of Prussia, PA). Ethylisopropyl amiloride (EIPA) was obtained from Merck Sharp and Dohme. Ouabain and all other chemicals were from Sigma. [3H]Ouabain (specific activity, 20 Ci/mmol; 1 Ci = 37 GBq), [3H]thymidine (specific activity, 15 Ci/mmol), and 22NaCl (specific activity, 100-1000 mCi per mg of sodium) were from Amersham.Cells. LLC-PK1 ...

show abstract

Kidney and Calcitonin

Cited by 45 publications

References 40 publications

Distribution of calcitonin-sensitive adenylate cyclase activity along the rabbit kidney tubule.

Distribution of calcitonin-sensitive adenylate cyclase activity along the rabbit kidney tubule.

Calcitonin and calcium ionophores: cyclic AMP responses in cells of a human lymphoid line.

Cell cycle-dependent and kinase-specific regulation of the apical Na/H exchanger and the Na,K-ATPase in the kidney cell line LLC-PK1 by calcitonin.

Contact Info

Product

Resources

About