WR-2721 inhibits parathyroid adenylate cyclase

Journal Article · Sun Feb 01 04:00:00 EST 1987 · Am. J. Physiol.; (United States)

OSTI ID:6409786

Weaver, M E; Morrissey, J; McConkey, C Jr; Goldfarb, S; Slatopolsky, E; Martin, K J

WR-2721 (S-2-(3-aminopropylamino)ethylphosphorothioic acid) is a chemoprotective and radioprotective agent that has been shown to lower serum calcium in dogs and in humans. This is secondary both to impaired release of CaS from bone and diminished secretion of parathyroid hormone (PTH) from parathyroid glands. Because cAMP plays a role in the regulation of PTH secretion and WR-2721 has been shown to lower cAMP levels in radiated mouse spleen, the authors investigated the effects of WR-2721 on cAMP production in dispersed bovine parathyroid cells. Additional, they studied the adenylate cyclase in plasma membranes from normal bovine parathyroid glands after exposure to WR-2721. With parathyroid cells incubated at 0.5 mM CaS , addition of Wr-2721 in concentrations ranging from 0.02 to 2.0 mM resulted in a progressive decrease in intracellular cAMP measured by radioimmunoassay. In plasma membranes of bovine parathyroid cells a dose-dependent decrease in adenylate cyclase activity was noted. Inhibition of the cyclase was seen over a wide range of MgS concentrations. WR-2721 inhibited both basal and NaF, Gpp(NH)(, forskolin, and pertussin toxin-stimulated adenylate cyclase. These data suggest that WR-2721 inhibits the activity of parathyroid adenylate cyclase.

• Research Organization: Washington Univ. School of Medicine, St. Louis, MO
• OSTI ID: 6409786
• Journal Information: Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States) Vol. 252:2; ISSN AJPHA
• Country of Publication: United States
• Language: English

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560300* -- Chemicals Metabolism & Toxicology
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALINE EARTH METAL COMPOUNDS
AMP
ANIMAL CELLS
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
CALCIUM COMPOUNDS
CATIONS
CATTLE
CELL CONSTITUENTS
CELL MEMBRANES
CHARGED PARTICLES
CYCLASES
DOMESTIC ANIMALS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENDOCRINE GLANDS
ENZYME ACTIVITY
ENZYMES
GLANDS
HORMONES
IMMUNOASSAY
IMMUNOLOGY
INHIBITION
IONS
ISOTOPE APPLICATIONS
KINETICS
LYASES
MAGNESIUM COMPOUNDS
MAMMALS
MEMBRANES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PARATHORMONE
PARATHYROID GLANDS
PEPTIDE HORMONES
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNOLOGY
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
RUMINANTS
THIOIC ACIDS
TRACER TECHNIQUES
VERTEBRATES