AJP - Endocrinology and Metabolism, Vol 252, Issue 2 E197-E201, Copyright © 1987 by American Physiological Society
WR-2721 inhibits parathyroid adenylate cyclase
M. E. Weaver, J. Morrissey, C. McConkey Jr, S. Goldfarb, E. Slatopolsky and K. J. Martin
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 Ca2+ 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, we investigated the effects of WR-2721 on cAMP
production in dispersed bovine parathyroid cells. Additionally, we 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 Ca2+, addition of WR-2721 in concentrations ranging from 0.02 to 2.0 mM
resulted in a progressive decrease in intracellular cAMP (42-50%,
respectively). 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 Mg2+ concentrations (2.5-40
mM). WR-2721 inhibited both basal and NaF, Gpp(NH)p, forskolin, and
pertussin toxin-stimulated adenylate cyclase. These data suggest that
WR-2721 inhibits the activity of parathyroid adenylate cyclase.
