Fluoride-induced changes in renal papillary cyclic-AMP

J. A. Maxwell; J. L. Caffrey; T. Yorio; R. J. Sinclair

doi:10.1016/0041-008X(83)90129-1

Fluoride-induced changes in renal papillary cyclic-AMP

J. A. Maxwell, J. L. Caffrey, T. Yorio, R. J. Sinclair

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Abstract

Studies were conducted which examined urinary excretion and papillary production of cyclic-AMP in the rat following vasopressin (ADH) stimulation in the presence or absence of inorganic fluoride ion (F). In one set of experiments, six anesthetized Fischer 344 rats were administered 5 munits arginine vasopressin during iv saline and sodium fluoride (NaF) infusions. Urinary cyclic-AMP concentration was unchanged by ADH but declined during NaF infusion, while urinary cyclic-AMP excretion rate was unchanged by ADH or ADH NaF. In a second set of experiments, 30 rats were divided into six groups of 5 each, and renal papilla and cortex were analyzed for cyclic-AMP. Group I was decapitated and not otherwise surgically manipulated. A second group had iv saline for 90 min while a third group had iv saline and ADH. A fourth group had isotonic NaF iv for 90 min and a fifth group had NaF and ADH. The results indicate that papillary cyclic-AMP is significantly increased by both ADH and NaF doses which did not cause changes in urinary cyclic-AMP excretion rates. We conclude from these experiments that determination of urinary cyclic-AMP concentration is not the best measure of vasopressin action and that tubular sensitivity to the hormone in the presence of F was better demonstrated by changes in papillary cyclic-AMP concentration. Further, it appears that the site of the biochemical renal lesion caused by F is at a site beyond the generation of cyclic-AMP.

Original language	English
Pages (from-to)	138-142
Number of pages	5
Journal	Toxicology and Applied Pharmacology
Volume	69
Issue number	1
DOIs	https://doi.org/10.1016/0041-008X(83)90129-1
State	Published - 15 Jun 1983

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10.1016/0041-008X(83)90129-1

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@article{ebf57f27b6c04ee4b340c8a931e17567,

title = "Fluoride-induced changes in renal papillary cyclic-AMP",

abstract = "Studies were conducted which examined urinary excretion and papillary production of cyclic-AMP in the rat following vasopressin (ADH) stimulation in the presence or absence of inorganic fluoride ion (F). In one set of experiments, six anesthetized Fischer 344 rats were administered 5 munits arginine vasopressin during iv saline and sodium fluoride (NaF) infusions. Urinary cyclic-AMP concentration was unchanged by ADH but declined during NaF infusion, while urinary cyclic-AMP excretion rate was unchanged by ADH or ADH NaF. In a second set of experiments, 30 rats were divided into six groups of 5 each, and renal papilla and cortex were analyzed for cyclic-AMP. Group I was decapitated and not otherwise surgically manipulated. A second group had iv saline for 90 min while a third group had iv saline and ADH. A fourth group had isotonic NaF iv for 90 min and a fifth group had NaF and ADH. The results indicate that papillary cyclic-AMP is significantly increased by both ADH and NaF doses which did not cause changes in urinary cyclic-AMP excretion rates. We conclude from these experiments that determination of urinary cyclic-AMP concentration is not the best measure of vasopressin action and that tubular sensitivity to the hormone in the presence of F was better demonstrated by changes in papillary cyclic-AMP concentration. Further, it appears that the site of the biochemical renal lesion caused by F is at a site beyond the generation of cyclic-AMP.",

author = "Maxwell, {J. A.} and Caffrey, {J. L.} and T. Yorio and Sinclair, {R. J.}",

note = "Funding Information: The polyuric response to elevated concentrations of inorganic fluoride ion (F) in the extracellular fluid has been well documented (Frascino, 1972; Mazze et al., 1972; Wallin and Kaplan, 1977) but the site and mechanism of the lesion have not been established. This failure to concentrate urine suggests that F may interfere with the action of vasopressin on the collecting tubule (Mazze et al., 1972; Wallin and Kaplan, 1977). Increased concentrations of cyclic-AMP in the collecting tubule have been associated with the water permeability response to vasopressin (Orloff and Handler, 1964). Wallin and Kaplan ( 1977) suggested that based on decreased urinary cyclic-AMP excretion in the presence of F in I This work was supported in part by National pathic Foundation Grant 80-I I-3 16.",

year = "1983",

month = jun,

day = "15",

doi = "10.1016/0041-008X(83)90129-1",

language = "English",

volume = "69",

pages = "138--142",

journal = "Toxicology and Applied Pharmacology",

issn = "0041-008X",

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number = "1",

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T1 - Fluoride-induced changes in renal papillary cyclic-AMP

AU - Maxwell, J. A.

AU - Caffrey, J. L.

AU - Yorio, T.

AU - Sinclair, R. J.

N1 - Funding Information: The polyuric response to elevated concentrations of inorganic fluoride ion (F) in the extracellular fluid has been well documented (Frascino, 1972; Mazze et al., 1972; Wallin and Kaplan, 1977) but the site and mechanism of the lesion have not been established. This failure to concentrate urine suggests that F may interfere with the action of vasopressin on the collecting tubule (Mazze et al., 1972; Wallin and Kaplan, 1977). Increased concentrations of cyclic-AMP in the collecting tubule have been associated with the water permeability response to vasopressin (Orloff and Handler, 1964). Wallin and Kaplan ( 1977) suggested that based on decreased urinary cyclic-AMP excretion in the presence of F in I This work was supported in part by National pathic Foundation Grant 80-I I-3 16.

PY - 1983/6/15

Y1 - 1983/6/15

N2 - Studies were conducted which examined urinary excretion and papillary production of cyclic-AMP in the rat following vasopressin (ADH) stimulation in the presence or absence of inorganic fluoride ion (F). In one set of experiments, six anesthetized Fischer 344 rats were administered 5 munits arginine vasopressin during iv saline and sodium fluoride (NaF) infusions. Urinary cyclic-AMP concentration was unchanged by ADH but declined during NaF infusion, while urinary cyclic-AMP excretion rate was unchanged by ADH or ADH NaF. In a second set of experiments, 30 rats were divided into six groups of 5 each, and renal papilla and cortex were analyzed for cyclic-AMP. Group I was decapitated and not otherwise surgically manipulated. A second group had iv saline for 90 min while a third group had iv saline and ADH. A fourth group had isotonic NaF iv for 90 min and a fifth group had NaF and ADH. The results indicate that papillary cyclic-AMP is significantly increased by both ADH and NaF doses which did not cause changes in urinary cyclic-AMP excretion rates. We conclude from these experiments that determination of urinary cyclic-AMP concentration is not the best measure of vasopressin action and that tubular sensitivity to the hormone in the presence of F was better demonstrated by changes in papillary cyclic-AMP concentration. Further, it appears that the site of the biochemical renal lesion caused by F is at a site beyond the generation of cyclic-AMP.

AB - Studies were conducted which examined urinary excretion and papillary production of cyclic-AMP in the rat following vasopressin (ADH) stimulation in the presence or absence of inorganic fluoride ion (F). In one set of experiments, six anesthetized Fischer 344 rats were administered 5 munits arginine vasopressin during iv saline and sodium fluoride (NaF) infusions. Urinary cyclic-AMP concentration was unchanged by ADH but declined during NaF infusion, while urinary cyclic-AMP excretion rate was unchanged by ADH or ADH NaF. In a second set of experiments, 30 rats were divided into six groups of 5 each, and renal papilla and cortex were analyzed for cyclic-AMP. Group I was decapitated and not otherwise surgically manipulated. A second group had iv saline for 90 min while a third group had iv saline and ADH. A fourth group had isotonic NaF iv for 90 min and a fifth group had NaF and ADH. The results indicate that papillary cyclic-AMP is significantly increased by both ADH and NaF doses which did not cause changes in urinary cyclic-AMP excretion rates. We conclude from these experiments that determination of urinary cyclic-AMP concentration is not the best measure of vasopressin action and that tubular sensitivity to the hormone in the presence of F was better demonstrated by changes in papillary cyclic-AMP concentration. Further, it appears that the site of the biochemical renal lesion caused by F is at a site beyond the generation of cyclic-AMP.

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U2 - 10.1016/0041-008X(83)90129-1

DO - 10.1016/0041-008X(83)90129-1

M3 - Article

C2 - 6304940

AN - SCOPUS:0020524803

SN - 0041-008X

VL - 69

SP - 138

EP - 142

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

IS - 1

ER -

Fluoride-induced changes in renal papillary cyclic-AMP

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