H-7 disrupts the actin cytoskeleton and increases outflow facility

Arch Ophthalmol. 1998 May;116(5):633-43. doi: 10.1001/archopht.116.5.633.

Abstract

Objectives: To determine the effects of the serine-threonine kinase inhibitor H-7 on (1) cell junctions and the attached actin-based cytoskeleton in cultured bovine aortic endothelial cells, and (2) outflow facility in living monkeys.

Methods: Bovine aortic endothelial cells were cultured by standard techniques. The architecture and distribution of actin filaments, vinculin, and beta-catenin in bovine aortic endothelial cells were studied by immunolabeling before and after exposure to H-7 at various concentrations and durations. Outflow facility (perfusion) and intraocular pressure (Goldmann tonometer) were determined before and after the intracameral or topical administration of H-7 or a vehicle.

Results: In bovine aortic endothelial cells, exposure to H-7 produced a reversible time- and concentration-dependent disruption of actin microfilaments and an alteration in the organization of cell-cell and cell-matrix adhesions. In monkeys, intracameral and topical administration of H-7 dose dependently and reversibly doubled facility, and topical H-7 reduced intraocular pressures.

Conclusion: H-7 increases outflow facility in monkeys, probably by inhibiting cell contractility, cytoskeletal support, and cell-cell adhesions in the trabecular meshwork.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology*
  • Actins / metabolism*
  • Administration, Topical
  • Animals
  • Aorta
  • Aqueous Humor / metabolism*
  • Cattle
  • Cell Adhesion / drug effects
  • Cells, Cultured
  • Cytoskeleton / metabolism*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Fluorescent Antibody Technique, Indirect
  • Intercellular Junctions / drug effects
  • Intercellular Junctions / metabolism
  • Intraocular Pressure / drug effects*
  • Macaca fascicularis
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Time Factors

Substances

  • Actins
  • Enzyme Inhibitors
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Protein-Serine-Threonine Kinases