Parathyroid hormone induced calcium efflux from cultured bone is
mediated by protein kinase c translocation.
Sprague, Stuart M., Mordecai M. Popovtzer, Michal Dranitzki-Elhalel,
and Hanna Wald.
Section of Nephrology and Hypertension, Hadassah University
Hospital, Hebrew University, Jerusalem, 91120 Israel
APStracts 3:0149F, 1996.
Activation of adenyl cyclase is believed to be the major intracellular
mediator of bone resorption induced by parathyroid hormone (PTH),
prostaglandins and various bone resorbing cytokines. Studies have
demonstrated a dissociation between PTH induced bone resorption and
cyclic-AMP formation as well as suggesting a role of protein kinase C
(PKC) in mediating, in part, the actions of PTH. We therefore
investigated the relative contribution of the adenyl cyclase or PKC
signal transduction pathways in mediating the PTH induced net calcium
release from cultured neonatal calvariae, an in vitro model of bone
resorption. PTH caused a dose dependent increase in calcium efflux
from cultured bone and activated both cyclic-AMP and PKC. To
determine the role of each of these second messengers in mediating
PTH induced calcium release from bone, calvariae were preincubated
with either the adenylate cyclase inhibitor, SQ 22536, or the protein
kinase C inhibitor, staurosporine prior to coincubation with PTH.
Compared to control, PTH caused a significant calcium efflux, whereas
preincubation with SQ 22536 had no effect on basal calcium efflux and
partially inhibited the calcium efflux caused by PTH. In contrast
preincubation with staurosporine completely obliterated the PTH
induced calcium efflux. PTH is a potent stimulator of calcium release
and activates both the cyclic-AMP and PKC signal transduction
pathways in cultured bone. Inhibition of PTH stimulated PKC activity
completely abolished the PTH induced calcium efflux from calvariae,
whereas PTH induced calcium efflux persisted in spite of adenyl
cyclase inhibition. Thus, the bone resorbing effect of PTH appears to
be dependent predominantly on activation of PKC.
Received 24 July 1996; accepted in final form 19 August 1996.
APS Manuscript Number F301-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996