Inhibition of hormone-stimulated inositol phosphate production and disruption of cytoskeletal structure. Effects of okadaic acid, microcystin, chlorpromazine, W7 and nystatin.
Inhibition of protein phosphatases 2A and 1 by okadaic acid and microcystin leads to cytoskeletal disruption and formation of plasma membrane blebs (blebbing) in hepatocytes. This phenomenon is associated to a marked inhibition of receptor-mediated and G-protein-mediated phosphoinositide turnover in rat hepatocytes. Other cytoskeletal-disrupting drugs such as chlorpromazine, W7 and nystatin mimic the effect of these protein phosphatase inhibitors on phosphoinositide metabolism and blebbing. Our data suggest that the coupling between G-protein and phospholipase C might be altered by cytoskeletal disruption.
Macías-Silva
M
M
Instituto de Fisiología Cellular, Universidad Nacional Autónoma de México, Méico, D.F.
García-Sáinz
J A
JA
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002746:Chlorpromazine / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000096:biosynthesis*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D052998:Microcystins; D009761:Nystatin / Q000494:pharmacology; D019319:Okadaic Acid / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; D052998:Microcystins; D010456:Peptides, Cyclic; D013449:Sulfonamides; D014665:Vasodilator Agents; D009761:Nystatin; D019319:Okadaic Acid; C017967:W 7; C078588:microcystin; D015544:Inositol 1,4,5-Trisphosphate; D002746:Chlorpromazine