Protein kinase C inhibition blocks the early appearance of vestibular compensation.
This study tests the hypothesis that activation of protein kinase C (PKC) is a critical step for early recovery from spontaneous nystagmus after unilateral ablation of the vestibular periphery. Halothane-NO(2)-O(2)-anesthetized Long-Evans rats received a 5-microl intracerebroventricular bolus of vehicle (distilled water, six rats), PKC inhibitor [Iso-H-7 (10 mM, four rats; 50 mM, five rats) or bisindolemaleimide I (Bis-I, 10 microM six rats)], PKG and PKA inhibitor (A-3, 1 mM, six rats), or the serine-threonine protein kinase inhibitor H-7 (1 mM, five rats; 10 mM, five rats). Surgical unilateral labyrinthectomy (UL) was completed within 15 min. Sham control groups showed no nystagmus. Bis-I and Iso-H-7 significantly retarded the disappearance of spontaneous nystagmus quick phases for 8 h after UL (p<0.05). The effects of Iso-H-7 were dose-dependent: more nystagmus quick phases (p<0.05) were present in the 50 mM than the 10 mM group at 7 and 8 h post-UL. The rats given A-3 showed a delayed retardation of nystagmus loss, which differed significantly (p<0.05) from controls at 4-8 h after labyrinthectomy. The number of nystagmus quick phases was significantly greater than controls (p<0. 05) in the 10 mM H-7 group at 4, 5, 6 and 48 h post-UL, but only at 6 and 24 h post-UL in the 1 mM H-7 group. Thus, PKC activation is an important early requirement for vestibular compensation during the acute post-labyrinthectomy period, while cyclic-nucleotide dependent kinases may be important in a later time frame.
Balaban
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CD
Department of Otolaryngology, University of Pittsburgh School of Medicine, 203 Lothrop Street, Pittsburgh, PA 15213, USA. cbalaban@vms.cis.pitt.edu
Freilino
M
M
Romero
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GG
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D007758:Ear, Inner / Q000502:physiology* / Q000601:surgery; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D009759:Nystagmus, Pathologic / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011689:Purkinje Cells / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; C080501:1-(5-isoquinolinylsulfonyl)-3-methylpiperazine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; C070515:bisindolylmaleimide I