title: Effect of cytochalasin-B on the metabolism of polyphosphoinositides in andrenocortical cells.
abstract: 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 studied the effects of cytochalasin-B and chaetoglobosin-C on polyphosphoinositide metabolism in myo-[3H]inositol-prelabeled frog interrenal (adrenal) 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 microfilaments, whereas chaetoglobosin-C, a cytochalasin analog that cannot interact with actin, did not modify the organization of the microfilament network. Cytochalasin-B caused a dramatic inhibition of corticosteroid release from perifused frog interrenal slices, whereas chaetoglobosin-C did not affect steroid secretion. Analysis of labeled inositol phosphates and phosphoinositides revealed that cytochalasin-B, but not chaetoglobosin-C, caused a significant increase in tritiated inositol content (+38%) and concurrently inhibited the formation of polyphosphoinositides (-48%). Cytochalasin-B reduced the production of phosphatidylinositol (-63%), phosphatidylinositol monophosphate (-46%), phosphatidylinositol bisphosphate (-46%), and lyso-phosphatidylinositol (-66%). Cytochalasin-B also blocked the stimulatory effect of angiotensin-II on the breakdown of phosphatidylinositol, phosphatidylinositol monophosphate, and phosphatidylinositol bisphosphate and the formation of lyso-phosphatidylinositol and inositol phosphates. The present results provide evidence of a role for microfilaments in polyphosphoinositide metabolism in adrenocortical cells. These data indicate that microfilaments are required for the incorporation of inositol into membrane phospholipids and are necessary for angiotensin-II-induced phospholipase activation.
authors.affiliation: European Institute for Peptide Research, Laboratory of Molecular Endocrinology, CNRS URA 650, UA INSERM, University of Rouen, Mont-Saint-Aignan, France.
authors.forename: M
authors.initials: M
authors.lastname: Feuilloley
authors.forename: L
authors.initials: L
authors.lastname: Desrues
authors.forename: H
authors.initials: H
authors.lastname: Vaudry
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism; D003571:Cytochalasin B / Q000494:pharmacology*; D026121:Indole Alkaloids; D007211:Indoles / Q000494:pharmacology; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D011895:Rana ridibunda
chemical_list: D026121:Indole Alkaloids; D007211:Indoles; D008246:Lysophospholipids; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C025449:lysophosphatidylinositol; D000804:Angiotensin II; D003571:Cytochalasin B; D000450:Aldosterone; C019290:chaetoglobosins; D003345:Corticosterone