Pharmacological evidence for a lack of role for protein kinase C in staurosporine-induced morphological changes in embryonic Xenopus myocytes.
Staurosporine, an inhibitor of protein kinases, induced outgrowth of cultured embryonic Xenopus myocytes. The outgrowing membrane elicited by staurosporine was stained uniformly with fluorescein isothiocyanate-phalloidin. Pretreatment with microfilament-disrupting agents but not microtubule inhibitors inhibited staurosporine-induced membrane outgrowth. Microfilament assembly is thus required for the action of staurosporine. Protein kinase C activators did not antagonize the membrane outgrowing effect of staurosporine. Furthermore, none of H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride), H-8 (N[2-(methylamino)ethyl]-5-isoquinoline sulfonamide), sphingosine, phloretin, genistein or calmidazolium induced any significant morphological changes of embryonic myocytes, indicating that tyrosine kinases, protein kinase C, protein kinase A or calmodulin-dependent protein kinases may not be involved in the membrane outgrowing action of staurosporine. Total protein content of myocytes was not altered by staurosporine and protein or RNA synthesis inhibitors did not inhibit the membrane outgrowth induced by staurosporine. Furthermore, membrane outgrowth induced by staurosporine was less pronounced in older cultured myocytes or myocytes acutely isolated at later stages of tadpoles, indicating that there is different developmental susceptibility to the action of staurosporine.
Fu
W M
WM
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei.
Chen
S P
SP
Wang
S M
SM
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D048429:Cell Size; D002478:Cells, Cultured; D004594:Electrophysiology; D004625:Embryo, Nonmammalian; D005456:Fluorescent Dyes; D007546:Isoquinolines / Q000494:pharmacology; D009124:Muscle Proteins / Q000096:biosynthesis; D009132:Muscles / Q000166:cytology* / Q000196:embryology / Q000201:enzymology / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019311:Staurosporine; D014981:Xenopus
D000470:Alkaloids; D005456:Fluorescent Dyes; D007546:Isoquinolines; D009124:Muscle Proteins; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine