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Fluoride-induced changes in renal papillary cyclic-AMP.

J A Maxwell, J L Caffrey, T Yorio

Toxicology and Applied Pharmacology

|June 15, 1983

Summary

Vasopressin (ADH) and fluoride ion (F) affect cyclic-AMP levels in rats. Papillary cyclic-AMP increased with ADH and NaF, but urinary excretion did not, indicating fluoride

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Area of Science:

Nephrology
Endocrinology
Biochemistry

Background:

Vasopressin (ADH) plays a crucial role in regulating water balance and blood pressure.
Cyclic-AMP (cAMP) is a key second messenger in cellular signaling pathways, including those regulated by ADH.
Inorganic fluoride ions (F) are known to interfere with cellular processes, but their specific effects on ADH-mediated signaling in the kidney require further investigation.

Purpose of the Study:

To investigate the impact of vasopressin (ADH) stimulation on urinary excretion and papillary production of cyclic-AMP (cAMP) in rats.
To examine how the presence of inorganic fluoride ion (F) influences ADH-mediated cAMP signaling in the rat kidney.
To determine the most effective measure for assessing vasopressin action in the presence of fluoride.

Main Methods:

Two sets of experiments were conducted on anesthetized Fischer 344 rats.
Experiment 1: Rats received arginine vasopressin (ADH) during intravenous saline and sodium fluoride (NaF) infusions, with measurements of urinary cAMP concentration and excretion rate.
Experiment 2: Rats were divided into groups receiving saline, ADH, NaF, or NaF with ADH, followed by analysis of cAMP levels in renal papilla and cortex.

Main Results:

Urinary cAMP concentration did not change with ADH but decreased during NaF infusion; urinary cAMP excretion rate remained unchanged by ADH or ADH/NaF.
Papillary cAMP levels significantly increased with both ADH and NaF administration.
These increases in papillary cAMP occurred without corresponding changes in urinary cAMP excretion rates.

Conclusions:

Urinary cyclic-AMP concentration is not the optimal indicator of vasopressin (ADH) action, especially in the presence of fluoride.
Papillary cyclic-AMP concentration serves as a more sensitive measure of tubular sensitivity to ADH when fluoride is present.
Fluoride appears to induce a biochemical renal lesion at a site downstream from cAMP generation.

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