M. Feuilloley et al., EFFECT OF CYTOCHALASIN-B ON THE METABOLISM OF POLYPHOSPHOINOSITIDES IN ADRENOCORTICAL-CELLS, Endocrinology, 133(5), 1993, pp. 2319-2326
We have previously shown that microfilament-disrupting agents inhibit
steroid secretion by frog adrenocortical cells. To determine the role
of microfilaments in the process of corticosteroid production, we stud
ied the effects of cytochalasin-B and chaetoglobosin-C on polyphosphoi
nositide metabolism in myo-[H-3]inositol-prelabeled frog interrenal (a
drenal) slices. Immunocytochemical labeling of adrenocortical cells in
primary culture with actin antiserum showed that cytochalasin-B (5 x
10(-5) m) induced a complete and reversible disruption of microfilamen
ts, whereas chaetoglobosin-C, a cytochalasin analog that cannot intera
ct with actin, did not modify the organization of the microfilament ne
twork. Cytochalasin-B caused a dramatic inhibition of corticosteroid r
elease from perifused frog interrenal slices, whereas chaetoglobosin-C
did not affect steroid secretion. Analysis of labeled inositol phosph
ates and phosphoinositides revealed that cytochalasin-B, but not chaet
oglobosin-C, caused a significant increase in tritiated inositol conte
nt (+38%) and concurrently inhibited the formation of polyphosphoinosi
tides (48%). Cytochalasin-B reduced the production of phosphatidylinos
itol (63%), phosphatidylinositol monophosphate (-46%), phosphatidylino
sitol bisphosphate (-46%), and lyso-phosphatidylinositol (66%). Cytoch
alasin-B also blocked the stimulatory effect of angiotensin-II on the
breakdown of phosphatidylinositol, phosphatidylinositol monophosphate,
and phosphatidylinositol bisphosphate and the formation of lyso-phosp
hatidylinositol and inositol phosphates. The present results provide e
vidence of a role for microfilaments in polyphosphoinositide metabolis
m in adrenocortical cells. These data indicate that microfilaments are
required for the incorporation of inositol into membrane phospholipid
s and are necessary for angiotensin-II-induced phospholipase activatio
n.