Mechanism of phosphaturia elicited by administration of phosphonoformate in vivo

Journal Article · Tue Nov 01 04:00:00 EST 1988 · American Journal of Physiology; (USA)

OSTI ID:6252605

VanScoy, M; Loghman-Adham, M; Onsgard, M; Szczepanska-Konkel, M; Homma, Sumiko; Knox, F G; Dousa, T P ^[1]

---

1. Mayo Clinic, Rochester, MN (USA)

The authors examined whether phosphonoformate (PFA) can cause phosphaturia through its direct action on brush-border membrane (BBM) in vivo. Infusion of PFA or of parathyroid hormone (PTH) to thyroparathyroidectomized rats caused a marked increase in fractional excretion of phosphate without changes in excretion of Na{sup +} or of GFR. The PFA-induced phosphaturia was not accompanied by an increase in urinary adenosine-3{prime},5{prime}-cyclic monophosphate (cAMP); moreover, PFA added in vitro did not influence the PTH-sensitive adenylate cyclase and cAMP-phosphodiesterase in proximal convoluted tubules. In BBM vesicles (BBMV) from rats with PFA-elicited phosphaturia, neither the rate of Na{sup +}-P{sub i} symport nor Na{sup +}-dependent binding of ({sup 14}C)PFA on BBMV was changed, whereas in BBMV from PTH-infused rats the V{sub max} of Na{sup +}-P{sub i} symport decreased. PFA is almost completely ultrafiltrable; no metabolic transformation of PFA was detected after ({sup 14}C)PFA exposure to rat renal cortical slices, homogenate, or to blood. They conclude that PFA causes phosphaturia by direct inhibition of Na{sup +}-P{sub i} symport across BBM in proximal tubules, acting from the luminal side. Thus PFA (foscarnet) has a unique direct mechanism of phosphaturic effect, via its action on P{sub i} reabsorption in proximal tubules in vivo.

• OSTI ID: 6252605
• Journal Information: American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 255:5; ISSN 0002-9513; ISSN AJPHA
• Country of Publication: United States
• Language: English

Related Subjects

551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ABSORPTION
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACID SALTS
CLEARANCE
DAYS LIVING RADIOISOTOPES
EXCRETION
FORMATES
HOMEOSTASIS
HORMONES
ISOTOPES
KIDNEYS
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
MEDICINE
NUCLEI
ODD-ODD NUCLEI
ORGANS
PARATHORMONE
PEPTIDE HORMONES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
RADIOISOTOPES
RATS
RENAL CLEARANCE
RODENTS
SURGERY
THYROIDECTOMY
TUBULES
VERTEBRATES