The differential influence of protein kinase inhibitors on retinal arbor morphology and eye-specific stripes in the frog retinotectal system.
We investigated retinal axon morphology and eye-specific afferent termination zones in the optic tectum of three-eyed tadpoles that were chronically treated with protein kinase inhibitors. The kinase inhibitors sphingosine, H-7, and phorbol ester, which down-regulates protein kinase C with chronic exposure, were applied to the tecta in a slow release plastic, Elvax. In vivo protein phosphorylation assays in drug-treated tadpoles indicated that the treatments decreased 32P incorporation into some protein bands by as much as 60%. Although the drugs did not cause a desegregation of the eye-specific stripes, treated retinal axon arbors covered about half the area covered by untreated arbors or arbors treated with inactive analogs of the drugs. We conclude that eye-specific segregation can be maintained under conditions that markedly alter retinal ganglion cell axon arbor size and that significantly perturb protein phosphorylation. Furthermore, we conclude that the protein kinase(s) that we blocked with these treatments is involved in the growth of axon arbors.
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Department of Molecular and Cellular Physiology, Stanford University Medical School, California 94305.
Constantine-Paton
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D006735:Horseradish Peroxidase; D007546:Isoquinolines / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D011145:Polyvinyls / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011894:Rana pipiens; D012160:Retina / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D013477:Superior Colliculi / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D014795:Visual Pathways / Q000187:drug effects / Q000502:physiology*
D007546:Isoquinolines; C064769:N-acetylsphingosine; D009419:Nerve Tissue Proteins; D010703:Phorbol Esters; D010879:Piperazines; D011145:Polyvinyls; D047428:Protein Kinase Inhibitors; C008876:phorbol-12,13-didecanoate; C016438:ethylenevinylacetate copolymer; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D006735:Horseradish Peroxidase; D013110:Sphingosine