RECONSTITUTION OF CALCIUM-REGULATED PARATHYROID-HORMONE SECRETION FROM STREPTOLYSIN-O-PERMEABILIZED PARATHYROID CELLS BY GUANOSINE 5'-O-(THIO)TRIPHOSPHATE
Lm. Matovcik et al., RECONSTITUTION OF CALCIUM-REGULATED PARATHYROID-HORMONE SECRETION FROM STREPTOLYSIN-O-PERMEABILIZED PARATHYROID CELLS BY GUANOSINE 5'-O-(THIO)TRIPHOSPHATE, Endocrinology, 138(3), 1997, pp. 1170-1179
Intracellular Ca2+ levels determine the amount of PTH secretion from p
arathyroid cells. Dissociated calf parathyroid cells were permeabilize
d with streptolysin-O (SLO) to provide an in vitro model system to exa
mine Ca2+-dependent regulation of hormone secretion. PTH release from
these cells was energy dependent and increased by cytosolic cofactors.
Guanosine 5'-O-(thio)triphosphate (GTP gamma S) increased PTH secreti
on from SLO-permeabilized cells in a dose-dependent manner from 0.1-10
0 mu M. In the absence of GTP-gamma S there mas no relationship betwee
n the ambient Ca2+ concentration and the rate of PTH secretion. Howeve
r, in the presence of GTP gamma S intracellular Ca2+ inhibited PTH sec
retion with an EC(50) of approximately 0.1 mu M, corresponding to phys
iological intracellular Ca2+ levels. Thus, the addition of GTP gamma S
to SLO-permeabilized parathyroid cells reconstituted the inverse rela
tionship between extracellular Ca2+ and PTH secretion that Is observed
in vivo and in intact cells. The data indicate that this effect is me
diated at least in part by heterotrimeric guanosine triphosphatases. I
n addition, calcium/calmodulin-dependent protein kinase II appears to
mediate low Ca2+-dependent PTH secretion from these cells.